Bi-allelic loss of ERGIC1 causes relatively mild arthrogryposis.
Clin Genet
; 100(3): 329-333, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-34037256
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrogripose
/
Proteínas de Transporte Vesicular
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Humans
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Infant
/
Male
Idioma:
En
Revista:
Clin Genet
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Suíça