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Title
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Pathogenic Homozygous Mutations in the DBT Gene (c.1174A>C) Result in Maple Syrup Urine Disease in a rs12021720 Carrier
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Type
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JournalPaper
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Keywords
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DBT gene, MSUD, mutation, rs12021720, BCKDHA gene, BCKDHB gene
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Abstract
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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.
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Researchers
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Morteza Alijanpour (Second Researcher), Erwin Brosens (Fourth Researcher), ُShima Soleimani Amiri (Third Researcher), omid Jazayeri (First Researcher)
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