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EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay

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 associ...

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Autores principales: Umair, Muhammad, Ballow, Mariam, Asiri, Abdulaziz, Alyafee, Yusra, al 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756316/
https://www.ncbi.nlm.nih.gov/pubmed/32869858
http://dx.doi.org/10.1111/cge.13842
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author Umair, Muhammad
Ballow, Mariam
Asiri, Abdulaziz
Alyafee, Yusra
al 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
author_facet Umair, Muhammad
Ballow, Mariam
Asiri, Abdulaziz
Alyafee, Yusra
al 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
author_sort Umair, Muhammad
collection PubMed
description 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.
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spelling pubmed-77563162020-12-28 EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay Umair, Muhammad Ballow, Mariam Asiri, Abdulaziz Alyafee, Yusra al 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 Clin Genet Original Articles 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. Blackwell Publishing Ltd 2020-09-15 2020-12 /pmc/articles/PMC7756316/ /pubmed/32869858 http://dx.doi.org/10.1111/cge.13842 Text en © 2020 The Authors. Clinical Genetics published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Umair, Muhammad
Ballow, Mariam
Asiri, Abdulaziz
Alyafee, Yusra
al 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
EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay
title EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay
title_full EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay
title_fullStr EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay
title_full_unstemmed EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay
title_short EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay
title_sort emc10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756316/
https://www.ncbi.nlm.nih.gov/pubmed/32869858
http://dx.doi.org/10.1111/cge.13842
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