Bi-allelic loss of ERGIC1 causes relatively mild arthrogryposis.
Clin Genet
; 100(3): 329-333, 2021 09.
Article
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arthrogryposis
/
Vesicular Transport Proteins
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Humans
/
Infant
/
Male
Language:
En
Journal:
Clin Genet
Year:
2021
Document type:
Article