مشخصات پژوهش

عنوان	Pathogenic Homozygous Mutations in the DBT Gene (c.1174A>C) Result in Maple Syrup Urine Disease in a rs12021720 Carrier
نوع پژوهش	مقاله چاپ شده
کلیدواژه‌ها	DBT gene, MSUD, mutation, rs12021720, BCKDHA gene, BCKDHB gene
چکیده	Objective: Maple syrup urine disease (MSUD; OMIM #248600) is an autosomal recessive metabolic disorder in the catabolism of branchedchain amino acids (leucine, isoleucine, and valine) and may be lethal if untreated in affected newborns. Methods: Single-nucleotide polymorphism haplotyping and Sanger sequencing of BCKDHA, BCKDHB, and DBT genes were performed in a cohort of 10 MSUD patients. Results: We identifed a 16.6 Mb homozygous region harboring the DBT gene in an Iranian girl presenting with MSUD. Sanger sequencing revealed a pathogenic homozygous variant (NM_001918.3: c.1174A > C) in the DBT gene. We further found a controversial variant (rs12021720: c.1150 A > G) in the DBT gene. This substitution (p.Ser384Gly) is highly debated in literature. Bioinformatics and cosegregation analysis, along with identifying the real pathogenic variants (c.1174 A > C), lead to terminate these various interpretations of c.1150 A > G variant. Conclusion: Our study introduced c.1150 A > G as a polymorphic variant, which is informative for variant databases and also helpful in molecular diagnosis.
پژوهشگران	مرتضی علیجانپور (نفر دوم)، اروین بروزنز (نفر چهارم)، شیما سلیمانی امیری (نفر سوم)، امید جزایری (نفر اول)