Bi-allelic loss of ERGIC1 causes relatively mild arthrogryposis.
ERGIC1
arthrogryposis
loss of function mutation
whole genome sequencing
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
18
05
2021
received:
31
03
2021
accepted:
19
05
2021
pubmed:
27
5
2021
medline:
27
1
2022
entrez:
26
5
2021
Statut:
ppublish
Résumé
Arthrogryposis describes the presence of multiple joint-contractures. Clinical severity of this phenotype is variable, and more than 400 causative genes have been proposed. Among these, ERGIC1 is a recently reported candidate encoding a putative transmembrane protein of the ER-Golgi interface. Two homozygous missense variants have been reported in patients with relatively mild non-syndromic arthrogryposis. In a consanguineous family with two affected siblings presenting congenital arthrogryposis and some facial dysmorphism we performed prenatal array-CGH, postnatal targeted exome and genome sequencing. Genome sequencing identified a homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1. mRNA quantification showed the complete absence of ERGIC1 expression in the two affected siblings and a decrease in heterozygous parents. Our observations validate the pathogenic role of ERGIC1 in congenital arthrogryposis and demonstrate that complete loss of function causes a relatively mild phenotype. These findings will contribute to improve genetic counseling of ERGIC1 mutations.
Identifiants
pubmed: 34037256
doi: 10.1111/cge.14004
pmc: PMC8453841
doi:
Substances chimiques
ERGIC1 protein, human
0
RNA, Messenger
0
Vesicular Transport Proteins
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
329-333Subventions
Organisme : Fondation Privée des HUG
ID : QS05-28
Informations de copyright
© 2021 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
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