Exploring molecular spectrum in thai patients with maple syrup urine disease: unveiling a common variant.

Autor: Lakkhana P; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Tim-Aroon T; Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. thipwimol.tim@mahidol.ac.th., Khongkraparn A; Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Noojarern S; Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Wongkittichote P; Division of Epidemiology and Translational Research, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Wichajarn K; Division of Medical Genetics, Department of Pediatrics, Srinagarind Hospital, Khon Kaen, Thailand., Kuptanon C; Division of Medical Genetics, Department of Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, Thailand., Boonyawat B; Division of Medical Genetics, Department of Pediatrics, Phramongkutklao Hospital, Bangkok, Thailand., Suphapeetiporn K; Department of Pediatrics, Faculty of Medicine, Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok, Thailand., Wejaphikul K; Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand., Seo G; Division of Medical Genetics, 3Billion Inc., Seoul, South Korea., Wattanasirichaigoon D; Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Jazyk: angličtina
Zdroj: Orphanet journal of rare diseases [Orphanet J Rare Dis] 2024 Oct 25; Vol. 19 (1), pp. 396. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1186/s13023-024-03411-7
Abstrakt: Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by variants in any of the following genes: BCKDHA, BCKDHB, and DBT gene. Previous reports have highlighted a variety of common causing genes and variants among different ethnic groups affected by MSUD. This study is the first to describe the molecular characteristics, potential common variants, clinical phenotypes, and treatment outcomes of 20 Thai MSUD patients before the implementation of expanded newborn screening in Thailand.
Results: A cross-sectional, multicenter study was conducted, including twenty Thai MSUD patients from 1997 to 2023. Most of the patients presented with classic neonatal onset (95%). The mortality rate was 20%, while global developmental delay was observed in 40% of the patients. Variants in the BCKDHB gene were detected in 85% (17/20) of the patients, while the BCKDHA gene accounted for 15% (3/20). The study identified the 11-kb deletion involving 5'UTR, exon 1, and intron 1 in the BCKDHB gene, from a position of g.80102385 to g.80113453 (NC_000006.12), accounting for 50% of all variants (20/40 alleles) in Thai MSUD patients. All patients with the 11-kb deletion in BCKDHB presented with the classic type. The gap-PCR for this common deletion was established in the study.
Conclusion: This study is the first to describe the clinical and molecular spectrum of Thai MSUD patients before the implementation of expanded NBS. The 11-kb deletion involving exon 1 in the BCKDHB emerges as the most common variant among Thai individuals with MSUD. Furthermore, the gap-PCR test for detecting the 11-kb exon 1 deletion status holds the potential for integration into stepwise molecular analysis following positive expanded newborn screening.
(© 2024. The Author(s).)
Databáze: MEDLINE
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