Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia.

Autor:	Alaamery M; Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia.; Saudi Genome Program, National Centre for Genomic Technologies, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.; KACST-BWH Centre of Excellence for Biomedicine, Joint Centres of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia., Massadeh S; Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia.; Saudi Genome Program, National Centre for Genomic Technologies, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.; KACST-BWH Centre of Excellence for Biomedicine, Joint Centres of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia., Aldarwish M; Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children's Hospital (KASCH), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia., Albesher N; Saudi Genome Program, National Centre for Genomic Technologies, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.; Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Aljawini N; KACST-BWH Centre of Excellence for Biomedicine, Joint Centres of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia., Alahmed O; Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia., Kashgari A; King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.; Department of Radiology, King Abdullah Specialized Children's Hospital, King Abdul Aziz Medical City, Riyadh, Saudi Arabia., Walsh CA; Division of Genetics and Genomics and Howard Hughes Medical Institute, Department of Pediatrics, Boston Children's Hospital, and Departments of Neurology and Pediatrics, Harvard Medical School, Boston, MA, United States., Eyaid W; Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children's Hospital (KASCH), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2024 Jan 16; Vol. 14, pp. 1294214. Date of Electronic Publication: 2024 Jan 16 (Print Publication: 2023).
DOI:	10.3389/fgene.2023.1294214
Abstrakt:	Congenital disorders of glycosylation (CDG) are a group of more than 100 rare genetic disorders characterized by impaired glycosylation of proteins and lipids. The clinical presentation of CDG varies tremendously, from single-organ to multi-organ involvement and from prenatal death to a normal adult phenotype. In this case study, we report a large consanguineous family with multiple children suffering from cerebral palsy, seizure, developmental and epileptic encephalopathy, and global developmental delay. Whole-exome sequencing (WES) analysis revealed a homozygous variant in the UDP-glucose dehydrogenase ( UGDH ) gene (c.950G>A; p.R317Q) which segregates with the familial phenotype with a plausible autosomal recessive mode of inheritance, indicating a potential disease-causing association. The UGDH gene encodes the UDP-glucose dehydrogenase, a key enzyme in the synthesis of specific extracellular matrix constituents (proteoglycans and glycolipids) involved in neural migration and connectivity during early brain development. Many pathogenic mutations of UGDH have been reported in recent literature works. However, the variant identified in this study has been observed only in the Saudi population (13 families) and not in any other ethnic background, suggesting that it may be an ancient founder mutation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Alaamery, Massadeh, Aldarwish, Albesher, Aljawini, Alahmed, Kashgari, Walsh and Eyaid.)
Databáze:	MEDLINE
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