EMC10 Homozygous Variant Identified in a Family with Global Developmental Delay, Mild Intellectual Disability, and Speech Delay.
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2021-09-02
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ArticleAuthors
Umair, Muhammad
Ballow, Mariam
Asiri, Abdulaziz
Alyafee, Yusra
Al Tuwaijri, Abeer
Alhamoudi, Kheloud M
Aloraini, Taghrid
Abdelhakim, Marwa
Althagafi, Azza Th.

Kafkas, Senay
Alsubaie, Lamia
Alrifai, Muhammad Talal
Hoehndorf, Robert

Alfares, Ahmed

Alfadhel, Majid

KAUST Department
Bio-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
Date
2020-09-15Online Publication Date
2020-09-15Print Publication Date
2020-12Embargo End Date
2021-09-02Submitted Date
2020-07-15Permanent link to this record
http://hdl.handle.net/10754/665018
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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. This article is protected by copyright. All rights reserved.Citation
Umair, 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.13842Sponsors
We would like to thank the patient and his family for their support.Publisher
WileyJournal
Clinical geneticsPubMed ID
32869858Additional Links
https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.13842ae974a485f413a2113503eed53cd6c53
10.1111/cge.13842
Scopus Count
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