EMC10 Homozygous Variant Identified in a Family with Global Developmental Delay, Mild Intellectual Disability, and Speech Delay.
Al Tuwaijri, Abeer
Alhamoudi, Kheloud M
Althagafi, Azza Th.
Alrifai, Muhammad Talal
KAUST DepartmentBio-Ontology Research Group (BORG)
Computational Bioscience Research Center (CBRC)
Computer Science Program
Computer, Electrical and Mathematical Sciences & Engineering Division, Computational Bioscience Research Center, King Abdullah University of Science and Technology
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Online Publication Date2020-09-15
Print Publication Date2020-12
Embargo End Date2021-09-02
Permanent link to this recordhttp://hdl.handle.net/10754/665018
MetadataShow full item record
AbstractIn 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. This article is protected by copyright. All rights reserved.
CitationUmair, M., Ballow, M., Asiri, A., Alyafee, Y., Al Tuwaijri, A., Alhamoudi, K. M., … Alfadhel, M. (2020). EMC10 Homozygous Variant Identified in a Family with Global Developmental Delay, Mild Intellectual Disability, and Speech Delay. Clinical Genetics. doi:10.1111/cge.13842
SponsorsWe would like to thank the patient and his family for their support.
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