Bi‐allelic loss of ERGIC1 causes relatively mild arthrogryposis. Issue 3 (14th June 2021)

• Record Type: Journal Article
• Authors: Marconi, Caterina; Lemmens, Laure; Masclaux, Frédéric; Mattioli, Francesca; Fluss, Joël; Extermann, Philippe; Mendez, Purificacion; Leuchter, Russia Ha‐Vinh; Stathaki, Elissavet; Laurent, Sacha; Hammar, Eva; Vannier, Anne; Varvagiannis, Konstantinos; Guipponi, Michel; Sloan‐Bena, Frédérique; Blouin, Jean‐Louis; Abramowicz, Marc; Fokstuen, Siv
• Is Part Of: Clinical genetics. Volume 100:Issue 3(2021)
• Page Start: 329
• Page End: 333
• Publication Date: 2021-06-14
• Subjects: arthrogryposis -- ERGIC1 -- loss of function mutation -- whole genome sequencing; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.14004
• Languages: English
• ISSNs: 0009-9163

Abstract

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. Abstract :