Premium
EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay
Author(s) -
Umair Muhammad,
Ballow Mariam,
Asiri Abdulaziz,
Alyafee Yusra,
Tuwaijri Abeer,
Alhamoudi Kheloud M.,
Aloraini Taghrid,
Abdelhakim Marwa,
Althagafi Azza Thamer,
Kafkas Senay,
Alsubaie Lamia,
Alrifai Muhammad Talal,
Hoehndorf Robert,
Alfares Ahmed,
Alfadhel Majid
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13842
Subject(s) - global developmental delay , sanger sequencing , exome sequencing , biology , genetics , gene , exome , mutation , phenotype
In recent years, several genes have been implicated in the variable disease presentation of global developmental delay (GDD) and intellectual disability (ID). The endoplasmic reticulum membrane protein complex (EMC) family is known to be involved in GDD and ID. Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders. EMC10 is a bone marrow‐derived angiogenic growth factor that plays an important role in infarct vascularization and promoting tissue repair. However, this gene has not been previously associated with human disease. Herein, we describe a Saudi family with two individuals segregating a recessive neurodevelopmental disorder. Both of the affected individuals showed mild ID, speech delay, and GDD. Whole‐exome sequencing (WES) and Sanger sequencing were performed to identify candidate genes. Further, to elucidate the functional effects of the variant, quantitative real‐time PCR (RT‐qPCR)‐based expression analysis was performed. WES revealed a homozygous splice acceptor site variant (c.679‐1G>A) in EMC10 (chromosome 19q13.33) that segregated perfectly within the family. RT‐qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients, indicating the pathogenicity of the identified variant. For the first time in the literature, the EMC10 gene variant was associated with mild ID, speech delay, and GDD. Thus, this gene plays a key role in developmental milestones, with the potential to cause neurodevelopmental disorders in humans.