The worldwide incidence of MSUD is estimated to be 1 in 185,000 live births however, in consanguineous ethnic groups, such as the Mennonite population, the incidence is as high as 1 in 380 live births ( Nellis et al., 2003 Puffenberger, 2003 Chuang et al., 2006). Maple syrup urine disease (MSUD, OMIM #248600) is an autosomal recessive inherited metabolic disorder, caused by a defective activity of the branched-chain α-keto acid dehydrogenase complex (BCKAD) complex in the mitochondria ( Chuang et al., 2004). In summary, this study reports a recombination mechanism in the BCKDHB gene causing a whole gene deletion in a newborn with MSUD. Hence, Alu-mediated non-allelic homologous recombination is speculated as the mutational event underlying the large deletion. The junction site of the deletion was localized within a homologous sequence in two AluYa5 elements. A novel 383,556 bp deletion (chr6: g.80811266_81194921del) was determined, which encompassed the entire BCKDHB gene. The deletion breakpoints were characterized using long-range PCR and sequencing. One allele presented a missense mutation (c.391G > A), while the other allele had a large deletion both were inherited from the patient’s unaffected parents. ![]() ![]() Compound heterozygous mutations in BCKDHB were identified in a Chinese patient with typical MSUD using next-generation sequencing, quantitative PCR, and array comparative genomic hybridization. Among the wide range of disease-causing mutations in BCKDHB, only one large deletion has been associated with MSUD. ![]() Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by mutations in the BCKDHA, BCKDHB, DBT, and DLD genes. 2Reproductive Genetic Center, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.1State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.Gang Liu 1† Dingyuan Ma 1† Ping Hu 1 Wen Wang 2 Chunyu Luo 1 Yan Wang 1 Yun Sun 1 Jingjing Zhang 1 Tao Jiang 1* Zhengfeng Xu 1*
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