Two homozygous mutations in the exon 5 of BCKDHB gene that may cause the classic form of maple syrup urine disease
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Maple syrup urine disease (MSUD) is a rare autosomal recessive genetic disorder caused by defects in the catabolism of the branched-chain amino acids (BCAAs). Classic form of MSUD (CMSUD) is caused by mutations in BCKDHA, BCKDHB, DBT genes mostly. In this study, we analyzed the clinical and genetic characteristics of two patients with CMSUD. Two homozygous mutations, c.517G > T (p.Asp173Tyr) and c.503G > A (p.Arg168His), both in the exon 5 of BCKDHB were detected respectively. The novel mutation p.Asp173Tyr of patient A, inherited from his parents, is predicted to affect conformation of protein by computer analysis. The reported mutation p.Arg168His observed in patient B seemed to occur in a maternal uniparental disomy inheritance manner. Review of related literature revealed that most missense mutations in exon 5 of BCKDHB in homozygous genotype often result in CMSUD because of its incorrect conformation, and exon 5 of BCKDHB might be a susceptible region. Thus the novel homozygous mutation p.Asp173Tyr and the founder homozygous mutation p.Arg168His may be responsible for the clinical presentation of the two CMSUD patients, facilitating the future genetic counselling and prenatal diagnosis.
KeywordsMaple syrup urine disease (MSUD) Branched-chain amino acids (BCAAs) BCKDHB gene
The study was supported by National “Twelfth Five-Year” Plan for Science and Technology Support (2012BAI09B04), China, and Health and Family planning Commission of Guangzhou Municipality Grant (20151A010048). Thank Dr. Lian Zhang and his team for the clinical data management.
Compliance with ethical standards
Conflict of interest statement
The authors declared that they have no conflicts of interest to this work.
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