Bi-allelic loss of <i>ERGIC1</i> causes relatively mild arthrogryposis

Article Article scientifique Article Bi-allelic loss of <i>ERGIC1</i> causes relatively mild arthrogryposis eng 2021-06-14 2021-09 author Marconi Caroline Baya Catherine 0000-0002-1210-3969 839212 author Lemmens Laure 672975 author Masclaux Frédéric 602759 author Mattioli Francesca author Fluss Joel Victor 28801 author Extermann Philippe 22851 author Mendez Purificacion 84285 author Ha Vinh Leuchter Elisa Russia Tuyet Mai 710706 author Stathaki Elissavet 691247 author Laurent Sacha 931717 author Hammar Bouveret Eva 86178 author Vannier Anne 751929 author Varvagiannis Konstantinos 781131 author Guipponi Michel 118157 author Sloan Bena Frédérique 629243 author Blouin Jean-Louis 513663 author Abramowicz Marc 0000-0003-0623-8768 884432 author Fokstuen Siv 133715 329-333 10.1111/cge.14004 34037256 0009-9163 PMC8453841 https://onlinelibrary.wiley.com/doi/10.1111/cge.14004 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. ERGIC1 Arthrogryposis Loss of function mutation Whole genome sequencing Dewey 616 Dewey 618 Dewey 576.5 Fondation Privée des HUG QS05-28 58 Département de pédiatrie, gynécologie et obstétrique 223 56 Département de médecine 221 135 Département de médecine génétique et développement 21D false 150 L'imagerie cérébrale 184 1297 Abramowicz Lab 1013 Clinical genetics 100 3 73474bde-56e1-4fba-ad1a-06abfab08034 Article (Published version) Public Article-scientifique-from-unpaywall.pdf 1156979 application/pdf CC BY-NC-ND-4.0 81d1a257-e152-4ff8-a8bb-a62d1628cf32 Appendix Public cge14004-sup-0001-supinfo.docx 256158 application/vnd.openxmlformats-officedocument.wordprocessingml.document openAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

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Bi-allelic loss of ERGIC1 causes relatively mild arthrogryposis	Clinical genetics			2021	171	114

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