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.
- A recurrent, homozygous EMC10 frameshift variant is associated with a syndrome of developmental delay with variable seizures and dysmorphic features.
- Authors: Shao DD, Straussberg R, Ahmed H, Khan A, Tian S, Hill RS, Smith RS, Majmundar AJ, Ameziane N, Neil JE, Yang E, Al Tenaiji A, Jamuar SS, Schlaeger TM, Al-Saffar M, Hovel I, Al-Shamsi A, Basel-Salmon L, Amir AZ, Rento LM, Lim JY, Ganesan I, Shril S, Evrony G, Barkovich AJ, Bauer P, Hildebrandt F, Dong M, Borck G, Beetz C, Al-Gazali L, Eyaid W, Walsh CA
- Issue date: 2021 Jun
- Mutated RAP1GDS1 causes a new syndrome of dysmorphic feature, intellectual disability & speech delay.
- Authors: Asiri A, Aloyouni E, Umair M, Alyafee Y, Al Tuwaijri A, Alhamoudi KM, Almuzzaini B, Al Baz A, Alwadaani D, Nashabat M, Alfadhel M
- Issue date: 2020 Jun
- Bi-allelic <i>TTC5</i> variants cause delayed developmental milestones and intellectual disability.
- Authors: Rasheed A, Gumus E, Zaki M, Johnson K, Manzoor H, LaForce G, Ross D, McEvoy-Venneri J, Stanley V, Lee S, Virani A, Ben-Omran T, Gleeson JG, Naz S, Schaffer A
- Issue date: 2021 Apr
- Whole exome sequencing is necessary to clarify ID/DD cases with de novo copy number variants of uncertain significance: Two proof-of-concept examples.
- Authors: Giorgio E, Ciolfi A, Biamino E, Caputo V, Di Gregorio E, Belligni EF, Calcia A, Gaidolfi E, Bruselles A, Mancini C, Cavalieri S, Molinatto C, Cirillo Silengo M, Ferrero GB, Tartaglia M, Brusco A
- Issue date: 2016 Jul
- Homozygous single base deletion in TUSC3 causes intellectual disability with developmental delay in an Omani family.
- Authors: Al-Amri A, Saegh AA, Al-Mamari W, El-Asrag ME, Ivorra JL, Cardno AG, Inglehearn CF, Clapcote SJ, Ali M
- Issue date: 2016 Jul