期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 113, 期 10, 页码 3122-3132出版社
WILEY-BLACKWELL
DOI: 10.1002/jcb.24189
关键词
MSUD; MUTATION; BCKDHA; BCKDHB; TRUNCATION
资金
- Department of Biotechnology, Government of India
- Council for Scientific and Industrial Research, Govt. of India
Maple Syrup Urine Disease is a rare metabolic disorder caused by reduced/absent activity of the branched chain a-Ketoacid dehydrogenase enzyme complex. Mutations in BCKDHA, BCKDHB, and DBT, that encode important subunits of the enzyme complex namely E1a, E1 beta, and E2, are the primary cause for the disease. We have performed the first molecular genetic analysis of MSUD from India on nine patients exhibiting classical MSUD symptoms. BCKDHA and BCKDHB mutations were identified in four and five patients, respectively including seven novel mutations namely the BCKDHA c.1249delC, c.1312T>C, and c.1561T>A and the BCKDHB c.401T>A, c.548G>A, c.964A>G, and c.1065delT. The BCKDHB c.970C>T (p.R324X) mutation was shown to trigger nonsense mediated decay-based degradation of the transcript. Seven of the total 11 mutations resulted in perturbations in the E1a or E1 beta C-termini either through altered termination or through an amino acid change; these are expected to result in disruption of E1 enzyme complex assembly. Our study has therefore revealed that BCKDHA and BCKDHB mutations might be primarily responsible for MSUD in the Indian population. J. Cell. Biochem. 113: 31223132, 2012. (c) 2012 Wiley Periodicals, Inc.
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