A Human Pleiotropic Multiorgan Condition Caused by Deficient Wnt Secretion.

Abnormalities, Multiple / genetics Animals Congenital Abnormalities / genetics Disease Models, Animal Fibroblasts / metabolism Gene Knock-In Techniques Genes, Recessive Genetic Pleiotropy Humans Intracellular Signaling Peptides and Proteins / genetics Mice Mice, Transgenic Mutation Pedigree Phenotype Receptors, G-Protein-Coupled / genetics Syndrome Wnt Proteins / metabolism Wnt Signaling Pathway

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
30 09 2021
Historique:
entrez: 29 9 2021
pubmed: 30 9 2021
medline: 30 10 2021
Statut: ppublish

Résumé

Structural birth defects occur in approximately 3% of live births; most such defects lack defined genetic or environmental causes. Despite advances in surgical approaches, pharmacologic prevention remains largely out of reach. We queried worldwide databases of 20,248 families that included children with neurodevelopmental disorders and that were enriched for parental consanguinity. Approximately one third of affected children in these families presented with structural birth defects or microcephaly. We performed exome or genome sequencing of samples obtained from the children, their parents, or both to identify genes with biallelic pathogenic or likely pathogenic mutations present in more than one family. After identifying disease-causing variants, we generated two mouse models, each with a pathogenic variant "knocked in," to study mechanisms and test candidate treatments. We administered a small-molecule Wnt agonist to pregnant animals and assessed their offspring. We identified homozygous mutations in Genetic variations affecting a central Wnt regulator caused syndromic structural birth defects. Results from mouse models suggest that what we have named Zaki syndrome is a potentially preventable disorder. (Funded by the National Institutes of Health and others.).

Sections du résumé

BACKGROUND
Structural birth defects occur in approximately 3% of live births; most such defects lack defined genetic or environmental causes. Despite advances in surgical approaches, pharmacologic prevention remains largely out of reach.
METHODS
We queried worldwide databases of 20,248 families that included children with neurodevelopmental disorders and that were enriched for parental consanguinity. Approximately one third of affected children in these families presented with structural birth defects or microcephaly. We performed exome or genome sequencing of samples obtained from the children, their parents, or both to identify genes with biallelic pathogenic or likely pathogenic mutations present in more than one family. After identifying disease-causing variants, we generated two mouse models, each with a pathogenic variant "knocked in," to study mechanisms and test candidate treatments. We administered a small-molecule Wnt agonist to pregnant animals and assessed their offspring.
RESULTS
We identified homozygous mutations in
CONCLUSIONS
Genetic variations affecting a central Wnt regulator caused syndromic structural birth defects. Results from mouse models suggest that what we have named Zaki syndrome is a potentially preventable disorder. (Funded by the National Institutes of Health and others.).

Identifiants

DOI: 10.1056/NEJMoa2033911 PMID: 34587386 PMC: PMC9017221
pubmed: 34587386
doi: 10.1056/NEJMoa2033911
pmc: PMC9017221
mid: NIHMS1790232
doi:

Substances chimiques

Gpr177 protein, mouse 0
Intracellular Signaling Peptides and Proteins 0
Receptors, G-Protein-Coupled 0
WLS protein, human 0
Wnt Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1292-1301

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS048453
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS098004
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM132120
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS047101
Pays : United States
Organisme : NICHD NIH HHS
ID : P01 HD104436
Pays : United States

Informations de copyright

Copyright © 2021 Massachusetts Medical Society.

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Auteurs

Guoliang Chai (G)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Emmanuelle Szenker-Ravi (E)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Changuk Chung (C)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Zhen Li (Z)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Lu Wang (L)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Muznah Khatoo (M)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Trevor Marshall (T)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Nan Jiang (N)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Xiaoxu Yang (X)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Jennifer McEvoy-Venneri (J)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Valentina Stanley (V)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Paula Anzenberg (P)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Nhi Lang (N)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Vanessa Wazny (V)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Jia Yu (J)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

David M Virshup (DM)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Rie Nygaard (R)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Filippo Mancia (F)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Rijad Merdzanic (R)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Maria B P Toralles (MBP)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Paula M L Pitanga (PML)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Ratna D Puri (RD)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Rebecca Hernan (R)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Wendy K Chung (WK)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Aida M Bertoli-Avella (AM)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Nouriya Al-Sannaa (N)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Maha S Zaki (MS)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Karl Willert (K)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Bruno Reversade (B)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).

Joseph G Gleeson (JG)

From the Rady Children's Institute for Genomic Medicine, San Diego (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., J.G.G.), and the University of California, San Diego, La Jolla (G.C., C.C., Z.L., L.W., T.M., N.J., X.Y., J.M.-V., V.S., P.A., N.L., K.W., J.G.G.) - both in California; Xuanwu Hospital, Capital Medical University, Beijing (G.C.); the Genome Institute of Singapore (E.S.-R., M.K., V.W., B.R.) and the Institute of Molecular and Cellular Biology (B.R.), Agency for Science, Technology, and Research, and the Program in Cancer and Stem Cell Biology, Duke-NUS (National University of Singapore) Medical School (J.Y., D.M.V.) - all in Singapore; the Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey (B.R.); the Department of Pediatrics, Duke University, Durham, NC (D.M.V.); the Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center (R.N., F.M.), and the Departments of Pediatrics and Medicine, Columbia University (R.H., W.K.C.) - both in New York; Centogene, Rostock, Germany (R.M., A.M.B.-A.); DNA Laboratório e Genética Médica, Salvador, Brazil (M.B.P.T., P.M.L.P.); the Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India (R.D.P.); Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia (N.A.-S.); and the Clinical Genetics Department, National Research Center, Cairo (M.S.Z.).
ORCID: 0000-0002-0889-9220

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Classifications MeSH

questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Malformations › Malformations multiples › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Eucaryotes › Animaux › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Malformations › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Ciblage de gène › Techniques de knock-in de gènes › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Gènes récessifs › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Pléiotropie › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Pedigree › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs couplés aux protéines G › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Maladie › Syndrome › A Human Pleiotropic Multiorgan Condition...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de type Wingless › A Human Pleiotropic Multiorgan Condition...
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