Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia
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...
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| Format: | Article |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1294214/full |
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| author | Manal Alaamery Manal Alaamery Manal Alaamery Salam Massadeh Salam Massadeh Salam Massadeh Manar Aldarwish Manar Aldarwish Nour Albesher Nour Albesher Nora Aljawini Othman Alahmed Amna Kashgari Amna Kashgari Christopher A. Walsh Wafaa Eyaid Wafaa Eyaid |
| author_facet | Manal Alaamery Manal Alaamery Manal Alaamery Salam Massadeh Salam Massadeh Salam Massadeh Manar Aldarwish Manar Aldarwish Nour Albesher Nour Albesher Nora Aljawini Othman Alahmed Amna Kashgari Amna Kashgari Christopher A. Walsh Wafaa Eyaid Wafaa Eyaid |
| author_sort | Manal Alaamery |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T13:50:01Z |
| format | Article |
| id | doaj.art-19c2de1afdd347e8b4a8a8815e3c9f16 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-08T13:50:01Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-19c2de1afdd347e8b4a8a8815e3c9f162024-01-16T04:20:58ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-01-011410.3389/fgene.2023.12942141294214Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi ArabiaManal Alaamery0Manal Alaamery1Manal Alaamery2Salam Massadeh3Salam Massadeh4Salam Massadeh5Manar Aldarwish6Manar Aldarwish7Nour Albesher8Nour Albesher9Nora Aljawini10Othman Alahmed11Amna Kashgari12Amna Kashgari13Christopher A. Walsh14Wafaa Eyaid15Wafaa Eyaid16Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi ArabiaSaudi Genome Program, National Centre for Genomic Technologies, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi ArabiaKACST-BWH Centre of Excellence for Biomedicine, Joint Centres of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi ArabiaDevelopmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi ArabiaSaudi Genome Program, National Centre for Genomic Technologies, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi ArabiaKACST-BWH Centre of Excellence for Biomedicine, Joint Centres of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi ArabiaGenetics 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 ArabiaKing Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre, Ministry of National Guard Health Affairs, Riyadh, Saudi ArabiaSaudi Genome Program, National Centre for Genomic Technologies, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi ArabiaFaculty of Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaKACST-BWH Centre of Excellence for Biomedicine, Joint Centres of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi ArabiaDevelopmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi ArabiaKing Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre, Ministry of National Guard Health Affairs, Riyadh, Saudi ArabiaDepartment of Radiology, King Abdullah Specialized Children’s Hospital, King Abdul Aziz Medical City, Riyadh, Saudi ArabiaDivision 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 StatesGenetics 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 ArabiaKing Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Centre, Ministry of National Guard Health Affairs, Riyadh, Saudi ArabiaCongenital 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.https://www.frontiersin.org/articles/10.3389/fgene.2023.1294214/fullUDP-glucose dehydrogenasewhole-exome sequencinggeneSaudiencephalopathymutation |
| spellingShingle | Manal Alaamery Manal Alaamery Manal Alaamery Salam Massadeh Salam Massadeh Salam Massadeh Manar Aldarwish Manar Aldarwish Nour Albesher Nour Albesher Nora Aljawini Othman Alahmed Amna Kashgari Amna Kashgari Christopher A. Walsh Wafaa Eyaid Wafaa Eyaid Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia Frontiers in Genetics UDP-glucose dehydrogenase whole-exome sequencing gene Saudi encephalopathy mutation |
| title | Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia |
| title_full | Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia |
| title_fullStr | Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia |
| title_full_unstemmed | Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia |
| title_short | Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia |
| title_sort | case report a founder ugdh variant associated with developmental epileptic encephalopathy in saudi arabia |
| topic | UDP-glucose dehydrogenase whole-exome sequencing gene Saudi encephalopathy mutation |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1294214/full |
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