Biallelic

Journal

Neurology. Genetics
ISSN: 2376-7839
Titre abrégé: Neurol Genet
Pays: United States
ID NLM: 101671068

Informations de publication

Date de publication:
Apr 2021
Historique:
received: 03 09 2020
accepted: 02 12 2020
entrez: 30 4 2021
pubmed: 1 5 2021
medline: 1 5 2021
Statut: epublish

Résumé

We aimed to identify pathogenic variants in a girl with epilepsy, developmental delay, cerebellar ataxia, oral motor difficulty, and structural brain abnormalities with the use of whole-exome sequencing. Whole-exome trio analysis and molecular functional studies were performed in addition to the clinical findings and neuroimaging studies. Brain MRI showed mild pachygyria, hypoplasia of the cerebellar vermis, and abnormal foliation of the cerebellar vermis, suspected for a variant in one of the genes of the Reelin pathway. Trio whole-exome sequencing and additional functional studies were performed to identify the pathogenic variants. Trio whole-exome sequencing revealed compound heterozygous splice variants in We conclude that these variants are very likely causally related to the cerebral phenotype and propose to consider loss-of-function

Identifiants

DOI: 10.1212/NXG.0000000000000558 PMID: 33928188 PMC: PMC7830234
pubmed: 33928188
doi: 10.1212/NXG.0000000000000558
pii: NG2020015727
pmc: PMC7830234
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e558

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS050375
Pays : United States

Informations de copyright

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Daphne J Smits (DJ)

Department of Clinical Genetics (D.J.S., R.S., M.W., M.S., G.M.S.M.), ErasmusMC University Medical Center Rotterdam; Department of Child Neurology (M.C.Y.W.) and Department of Radiology (M.H.G.D.), Sophia Children's Hospital, ErasmusMC University Medical Center Rotterdam, the Netherlands; Department of Pediatrics (W.B.D.), University of Washington; Department of Neurology (W.B.D.), University of Washington, Seattle; Center for Integrative Brain Research (W.B.D.), Seattle Children's Research Institute, WA; Department of Human Genetics (W.B.D.), University of Minnesota, Minneapolis; Department of Radiology and Biomedical Imaging (A.J.B.), University of California, San Francisco; and ENCORE Expertise Center for Neurodevelopmental Disorders (M.C.Y.W., M.H.G.D., G.M.S.M.), ErasmusMC University Medical Center, Rotterdam, the Netherlands.

Rachel Schot (R)

Department of Clinical Genetics (D.J.S., R.S., M.W., M.S., G.M.S.M.), ErasmusMC University Medical Center Rotterdam; Department of Child Neurology (M.C.Y.W.) and Department of Radiology (M.H.G.D.), Sophia Children's Hospital, ErasmusMC University Medical Center Rotterdam, the Netherlands; Department of Pediatrics (W.B.D.), University of Washington; Department of Neurology (W.B.D.), University of Washington, Seattle; Center for Integrative Brain Research (W.B.D.), Seattle Children's Research Institute, WA; Department of Human Genetics (W.B.D.), University of Minnesota, Minneapolis; Department of Radiology and Biomedical Imaging (A.J.B.), University of California, San Francisco; and ENCORE Expertise Center for Neurodevelopmental Disorders (M.C.Y.W., M.H.G.D., G.M.S.M.), ErasmusMC University Medical Center, Rotterdam, the Netherlands.

Martina Wilke (M)

Department of Clinical Genetics (D.J.S., R.S., M.W., M.S., G.M.S.M.), ErasmusMC University Medical Center Rotterdam; Department of Child Neurology (M.C.Y.W.) and Department of Radiology (M.H.G.D.), Sophia Children's Hospital, ErasmusMC University Medical Center Rotterdam, the Netherlands; Department of Pediatrics (W.B.D.), University of Washington; Department of Neurology (W.B.D.), University of Washington, Seattle; Center for Integrative Brain Research (W.B.D.), Seattle Children's Research Institute, WA; Department of Human Genetics (W.B.D.), University of Minnesota, Minneapolis; Department of Radiology and Biomedical Imaging (A.J.B.), University of California, San Francisco; and ENCORE Expertise Center for Neurodevelopmental Disorders (M.C.Y.W., M.H.G.D., G.M.S.M.), ErasmusMC University Medical Center, Rotterdam, the Netherlands.

Marjon van Slegtenhorst (M)

Department of Clinical Genetics (D.J.S., R.S., M.W., M.S., G.M.S.M.), ErasmusMC University Medical Center Rotterdam; Department of Child Neurology (M.C.Y.W.) and Department of Radiology (M.H.G.D.), Sophia Children's Hospital, ErasmusMC University Medical Center Rotterdam, the Netherlands; Department of Pediatrics (W.B.D.), University of Washington; Department of Neurology (W.B.D.), University of Washington, Seattle; Center for Integrative Brain Research (W.B.D.), Seattle Children's Research Institute, WA; Department of Human Genetics (W.B.D.), University of Minnesota, Minneapolis; Department of Radiology and Biomedical Imaging (A.J.B.), University of California, San Francisco; and ENCORE Expertise Center for Neurodevelopmental Disorders (M.C.Y.W., M.H.G.D., G.M.S.M.), ErasmusMC University Medical Center, Rotterdam, the Netherlands.

Marie Claire Y de Wit (MCY)

Department of Clinical Genetics (D.J.S., R.S., M.W., M.S., G.M.S.M.), ErasmusMC University Medical Center Rotterdam; Department of Child Neurology (M.C.Y.W.) and Department of Radiology (M.H.G.D.), Sophia Children's Hospital, ErasmusMC University Medical Center Rotterdam, the Netherlands; Department of Pediatrics (W.B.D.), University of Washington; Department of Neurology (W.B.D.), University of Washington, Seattle; Center for Integrative Brain Research (W.B.D.), Seattle Children's Research Institute, WA; Department of Human Genetics (W.B.D.), University of Minnesota, Minneapolis; Department of Radiology and Biomedical Imaging (A.J.B.), University of California, San Francisco; and ENCORE Expertise Center for Neurodevelopmental Disorders (M.C.Y.W., M.H.G.D., G.M.S.M.), ErasmusMC University Medical Center, Rotterdam, the Netherlands.

Marjolein H G Dremmen (MHG)

Department of Clinical Genetics (D.J.S., R.S., M.W., M.S., G.M.S.M.), ErasmusMC University Medical Center Rotterdam; Department of Child Neurology (M.C.Y.W.) and Department of Radiology (M.H.G.D.), Sophia Children's Hospital, ErasmusMC University Medical Center Rotterdam, the Netherlands; Department of Pediatrics (W.B.D.), University of Washington; Department of Neurology (W.B.D.), University of Washington, Seattle; Center for Integrative Brain Research (W.B.D.), Seattle Children's Research Institute, WA; Department of Human Genetics (W.B.D.), University of Minnesota, Minneapolis; Department of Radiology and Biomedical Imaging (A.J.B.), University of California, San Francisco; and ENCORE Expertise Center for Neurodevelopmental Disorders (M.C.Y.W., M.H.G.D., G.M.S.M.), ErasmusMC University Medical Center, Rotterdam, the Netherlands.

William B Dobyns (WB)

Department of Clinical Genetics (D.J.S., R.S., M.W., M.S., G.M.S.M.), ErasmusMC University Medical Center Rotterdam; Department of Child Neurology (M.C.Y.W.) and Department of Radiology (M.H.G.D.), Sophia Children's Hospital, ErasmusMC University Medical Center Rotterdam, the Netherlands; Department of Pediatrics (W.B.D.), University of Washington; Department of Neurology (W.B.D.), University of Washington, Seattle; Center for Integrative Brain Research (W.B.D.), Seattle Children's Research Institute, WA; Department of Human Genetics (W.B.D.), University of Minnesota, Minneapolis; Department of Radiology and Biomedical Imaging (A.J.B.), University of California, San Francisco; and ENCORE Expertise Center for Neurodevelopmental Disorders (M.C.Y.W., M.H.G.D., G.M.S.M.), ErasmusMC University Medical Center, Rotterdam, the Netherlands.

A James Barkovich (AJ)

Department of Clinical Genetics (D.J.S., R.S., M.W., M.S., G.M.S.M.), ErasmusMC University Medical Center Rotterdam; Department of Child Neurology (M.C.Y.W.) and Department of Radiology (M.H.G.D.), Sophia Children's Hospital, ErasmusMC University Medical Center Rotterdam, the Netherlands; Department of Pediatrics (W.B.D.), University of Washington; Department of Neurology (W.B.D.), University of Washington, Seattle; Center for Integrative Brain Research (W.B.D.), Seattle Children's Research Institute, WA; Department of Human Genetics (W.B.D.), University of Minnesota, Minneapolis; Department of Radiology and Biomedical Imaging (A.J.B.), University of California, San Francisco; and ENCORE Expertise Center for Neurodevelopmental Disorders (M.C.Y.W., M.H.G.D., G.M.S.M.), ErasmusMC University Medical Center, Rotterdam, the Netherlands.

Grazia M S Mancini (GMS)

Department of Clinical Genetics (D.J.S., R.S., M.W., M.S., G.M.S.M.), ErasmusMC University Medical Center Rotterdam; Department of Child Neurology (M.C.Y.W.) and Department of Radiology (M.H.G.D.), Sophia Children's Hospital, ErasmusMC University Medical Center Rotterdam, the Netherlands; Department of Pediatrics (W.B.D.), University of Washington; Department of Neurology (W.B.D.), University of Washington, Seattle; Center for Integrative Brain Research (W.B.D.), Seattle Children's Research Institute, WA; Department of Human Genetics (W.B.D.), University of Minnesota, Minneapolis; Department of Radiology and Biomedical Imaging (A.J.B.), University of California, San Francisco; and ENCORE Expertise Center for Neurodevelopmental Disorders (M.C.Y.W., M.H.G.D., G.M.S.M.), ErasmusMC University Medical Center, Rotterdam, the Netherlands.

Classifications MeSH