Reanalysis of clinical exome identifies the second variant in two individuals with recessive disorders.

Exome Phenotype Heterozygote Exome Sequencing

Journal

European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235

Informations de publication

Date de publication:
Jun 2023
Historique:
received: 25 10 2022
accepted: 12 01 2023
revised: 09 01 2023
pmc-release: 01 06 2024
medline: 12 6 2023
pubmed: 24 1 2023
entrez: 23 1 2023
Statut: ppublish

Résumé

Clinical exome/genome sequencing is increasingly being utilized by clinicians to diagnose various likely genetic conditions, but many cases remain undiagnosed. In a subset of those undiagnosed cases, a single heterozygous variant in an autosomal recessive (AR) condition with consistent phenotype may be identified, raising the question if a second variant is missing. Here, we report two cases of recessive conditions in which only one heterozygous variant was initially reported by clinical exome sequencing, and on research reanalysis a second heterozygous variant in trans was identified. We performed a review of the existing exome reanalysis literature and found that this aspect is often not emphasized. These findings highlight the importance of data reanalysis in undiagnosed cases where only a single disease-associated variant is identified in an AR condition with a strong link to presenting phenotype.

Identifiants

DOI: 10.1038/s41431-023-01291-2 PMID: 36690831 PMC: PMC10250359
pubmed: 36690831
doi: 10.1038/s41431-023-01291-2
pii: 10.1038/s41431-023-01291-2
pmc: PMC10250359
doi:

Types de publication

Review Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

712-715

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)
ID : U19HD077671
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : U54HD090255

Informations de copyright

© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.

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Auteurs

Qifei Li (Q)

Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Rohan Agrawal (R)

Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.

Klaus Schmitz-Abe (K)

Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Casie A Genetti (CA)

Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.

Melissa A Fernandes (MA)

Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.

Noah L Fryou (NL)

Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.

Jill A Madden (JA)

Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.

Catherine A Brownstein (CA)

Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-7371-0340

Edward C Smith (EC)

Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.

Farrah Rajabi (F)

Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Alan H Beggs (AH)

Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0001-8818-0568

Pankaj B Agrawal (PB)

Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA. pankaj.agrawal@enders.tch.harvard.edu.
Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA. pankaj.agrawal@enders.tch.harvard.edu.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA. pankaj.agrawal@enders.tch.harvard.edu.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA. pankaj.agrawal@enders.tch.harvard.edu.
Broad Institute of MIT and Harvard, Cambridge, MA, USA. pankaj.agrawal@enders.tch.harvard.edu.
ORCID: 0000-0003-3255-0456

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Exome › Reanalysis of clinical exome identifies the...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Reanalysis of clinical exome identifies the...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Hétérozygote › Reanalysis of clinical exome identifies the...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Séquençage de l'exome › Reanalysis of clinical exome identifies the...