A Novel Whole Gene Deletion of BCKDHB by Alu-Mediated Non-allelic Recombination in a Chinese Patient With Maple Syrup Urine Disease

Frontiers in Genetics

Wen Wang¹  Yun Sun²  Tao Jiang²  Ping Hu²  Chunyu Luo²  Gang Liu²  Yan Wang²  Jingjing Zhang²  Zhengfeng Xu²  Dingyuan Ma² 

[1] Reproductive Genetic Center, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China;State 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;

关键词: maple syrup urine disease;    BCKDHB;    dried blood spot;    novel mutation;    large deletion;   

DOI  :  10.3389/fgene.2018.00145

来源: DOAJ

【 摘 要 】

Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by mutations in the BCKDHA, BCKDHB, DBT, and DLD genes. Among the wide range of disease-causing mutations in BCKDHB, only one large deletion has been associated with MSUD. 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. 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. The deletion breakpoints were characterized using long-range PCR and sequencing. A novel 383,556 bp deletion (chr6: g.80811266_81194921del) was determined, which encompassed the entire BCKDHB gene. The junction site of the deletion was localized within a homologous sequence in two AluYa5 elements. Hence, Alu-mediated non-allelic homologous recombination is speculated as the mutational event underlying the large deletion. In summary, this study reports a recombination mechanism in the BCKDHB gene causing a whole gene deletion in a newborn with MSUD.

【 授权许可】

Unknown