Developmental genomics of limb malformations: Allelic series in association with gene dosage effects contribute to the clinical variability.
Alu/Alu-mediated rearrangement
SV mutagenesis
allelic series
birth defect
clinical genomics
congenital limb malformation
developmental genomics
exome sequencing analysis
gene dosage effect
limb development
Journal
HGG advances
ISSN: 2666-2477
Titre abrégé: HGG Adv
Pays: United States
ID NLM: 101772885
Informations de publication
Date de publication:
13 Oct 2022
13 Oct 2022
Historique:
received:
07
03
2022
accepted:
19
07
2022
entrez:
29
8
2022
pubmed:
30
8
2022
medline:
30
8
2022
Statut:
epublish
Résumé
Genetic heterogeneity, reduced penetrance, and variable expressivity, the latter including asymmetric body axis plane presentations, have all been described in families with congenital limb malformations (CLMs). Interfamilial and intrafamilial heterogeneity highlight the complexity of the underlying genetic pathogenesis of these developmental anomalies. Family-based genomics by exome sequencing (ES) and rare variant analyses combined with whole-genome array-based comparative genomic hybridization were implemented to investigate 18 families with limb birth defects. Eleven of 18 (61%) families revealed explanatory variants, including 7 single-nucleotide variant alleles and 3 copy number variants (CNVs), at previously reported "disease trait associated loci":
Identifiants
pubmed: 36035248
doi: 10.1016/j.xhgg.2022.100132
pii: S2666-2477(22)00048-3
pmc: PMC9403727
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100132Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
J.R.L. has stock ownership in 23andMe, is a paid consultant for the Regeneron Genetics Center, and is a co-inventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, genomic disorders, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing and genomic testing (ES, WGS, CMA, and aCGH) conducted at Baylor Genetics (BG). J.R.L. serves on the Scientific Advisory Board (SAB) of BG.
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