Bi-allelic loss-of-function variants in
nervous system diseases
neuromuscular diseases
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
27
06
2021
accepted:
14
10
2021
pubmed:
7
11
2021
medline:
28
12
2022
entrez:
6
11
2021
Statut:
ppublish
Résumé
Fetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We aimed to further define the set of genes involved. We performed in-depth clinical characterisation and exome sequencing on a cohort of 23 FA index cases sharing arthrogryposis as a common feature. We identified likely pathogenic or pathogenic variants in 12 different established disease genes explaining the disease phenotype in 13 index cases and report 12 novel variants. In the unsolved families, a search for recessive-type variants affecting the same gene was performed; and in five affected fetuses of two unrelated families, a homozygous loss-of-function variant in the Our study underlines the broad locus heterogeneity of FA with well-established and atypical genotype-phenotype associations. We describe
Sections du résumé
BACKGROUND
Fetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We aimed to further define the set of genes involved.
METHODS
We performed in-depth clinical characterisation and exome sequencing on a cohort of 23 FA index cases sharing arthrogryposis as a common feature.
RESULTS
We identified likely pathogenic or pathogenic variants in 12 different established disease genes explaining the disease phenotype in 13 index cases and report 12 novel variants. In the unsolved families, a search for recessive-type variants affecting the same gene was performed; and in five affected fetuses of two unrelated families, a homozygous loss-of-function variant in the
CONCLUSION
Our study underlines the broad locus heterogeneity of FA with well-established and atypical genotype-phenotype associations. We describe
Identifiants
pubmed: 34740919
pii: jmedgenet-2021-108064
doi: 10.1136/jmedgenet-2021-108064
pmc: PMC9811090
doi:
Substances chimiques
KIF21A protein, human
0
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
48-56Informations de copyright
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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