Pathogenic Homozygous Mutations in the DBT Gene (c.1174A>C) Result in Maple Syrup Urine Disease in a rs12021720 Carrier

Morteza Alijanpour, Omid Jazayeri*, Shima Soleimani Amiri, Erwin Brosens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)


OBJECTIVE: Maple syrup urine disease (MSUD; OMIM #248600) is an autosomal recessive metabolic disorder in the catabolism of branched-chain 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 identified 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.

Original languageEnglish
Pages (from-to)596-601
Number of pages6
JournalLaboratory Medicine
Issue number6
Publication statusPublished - Nov 2022

Bibliographical note

This work was a joint project and supported by the Babol University of
Medical Science, University of Mazandaran, and Babol Razi Pathobiology
and Genetic Center Diagnostic Laboratory.

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail:


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