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Biallelic loss of <scp><i>EMC10</i></scp> leads to mild to severe intellectual disability

Rauan Kaiyrzhanov, Clarissa Rocca, Mohnish Suri, S. A. Gulieva, Maha S. Zaki, Noa Zunz Henig, Karine Siquier-Pernet, Ulviyya Guliyeva, Samir Mounir, Daphna Marom, Aynur Allahverdiyeva, Hisham Megahed, Hans van Bokhoven, Vincent Cantagrel, Abolfazl Rad, Alemeh Pourkeramti, Boshra Dehghani, Diane D. Shao, Keren Markus‐Bustani, Efrat Sofrin‐Drucker, Naama Orenstein, Kamran Salayev, Filippo Arrigoni, Henry Houlden, Reza Maroofian

2022Annals of Clinical and Translational Neurology16 citationsDOIOpen Access PDF

Abstract

The endoplasmic reticulum membrane protein complex subunit 10 (EMC10) is a highly conserved protein responsible for the post-translational insertion of tail-anchored membrane proteins into the endoplasmic reticulum in a defined topology. Two biallelic variants in EMC10 have previously been associated with a neurodevelopmental disorder. Utilizing exome sequencing and international data sharing we have identified 10 affected individuals from six independent families with five new biallelic loss-of-function and one previously reported recurrent EMC10 variants. This report expands the molecular and clinical spectrum of EMC10 deficiency, provides a comprehensive dysmorphological assessment and highlights an overlap between the clinical features of EMC10-and EMC1-related disease.

Topics & Concepts

Endoplasmic reticulumExome sequencingLoss functionMedicineProtein subunitExomeFunction (biology)Computational biologyCell biologyBioinformaticsGeneticsGeneMutationBiologyPhenotypeGenetics and Neurodevelopmental DisordersGenomics and Rare DiseasesGlycogen Storage Diseases and Myoclonus
Biallelic loss of <scp><i>EMC10</i></scp> leads to mild to severe intellectual disability | Litcius