- 作者：Nan Yang ; Lianshu Han ; Xuefan Gu ; Jun Ye ; Wenjuan Qiu ; Huiwen Zhang ; Zhuwen Gong ; Yafen Zhang
- 关键词：Maple syrup urine disease ; Branched-chain ¦Á-keto acid dehydrogenase complex ; Gene mutation
- 刊名：Molecular Genetics and Metabolism
- 出版年：2012
- 出版时间：August, 2012
- 年：2012
- 卷：106
- 期：4
- 页码：412-418
- 全文大小：1214 K
Summary
Objective
Maple syrup urine disease (MSUD) is predominantly caused by mutations in the BCKDHA, BCKDHB and DBT genes, which encode for the E1¦Á, E1¦Â and E2 subunits of the branched-chain ¦Á-keto acid dehydrogenase complex, respectively. The aim of this study was to screen DNA samples from 16 Chinese MSUD patients and assess a potential correlation between genotype and phenotype.Methods
BCKDHA, BCKDHB and DBT genes were analyzed by polymerase chain reaction (PCR) and direct sequencing. Segments bearing novel mutations were identified by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis.
Results
Within the variant alleles, 28 mutations (28/32, 87.5 % ), were detected in 15 patients, while one patient displayed no mutations. Mutations were comprised of 20 different: 6 BCKDHA gene mutations in 4 cases, 10 BCKDHB gene mutations in 8 cases and 4 DBT gene mutations in 3 cases. From these, 14 were novel, which included 3 mutations in the BCKDHA gene, 7 in the BCKDHB gene and 4 in the DBT gene. Only two patients with mutations in the BCKDHB and DBT genes were thiamine-responsive and presented a better clinical outcome.
Conclusion
We identified 20 different mutations within the BCKDHA, BCKDHB and DBT genes among 16 Chinese MSUD patients, including 14 novel mutations. The majority were non-responsive to thiamine, associating with a worse clinical outcome. Our data provide the basis for further genotype-phenotype correlation studies in these patients, which will be beneficial for early diagnosis and in directing the approach to clinical intervention.