title: Two homozygous mutations in the exon 5 of BCKDHB gene that may cause the classic form of maple syrup urine disease.
abstract: 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.
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou women and children's medical center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong province, 510623, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou women and children's medical center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong province, 510623, China.
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Prenatal Diagnostic Center, Guangzhou women and children's medical center, Guangzhou Medical University, Guangzhou, 510623, China.
authors.forename: Fatao
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou women and children's medical center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong province, 510623, China.
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou women and children's medical center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong province, 510623, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou women and children's medical center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong province, 510623, China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou women and children's medical center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong province, 510623, China. liliuxia2010@foxmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D017809:Fatal Outcome; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008375:Maple Syrup Urine Disease / Q000000981:diagnostic imaging* / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*
chemical_list: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
keywords: BCKDHB gene; Branched-chain amino acids (BCAAs); Maple syrup urine disease (MSUD)