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Molecular genetic analysis of MSUD from India reveals mutations causing altered protein truncation affecting the C‐termini of E1α and E1β
Author(s) -
Bashyam Murali D.,
Chaudhary Ajay K.,
Sinha Manjari,
Nagarajaram H.A.,
Devi A. Radha Rama,
Bashyam Leena,
Reddy E. Chandrakanth,
Dalal Ashwin
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24189
Subject(s) - maple syrup urine disease , nonsense mutation , mutation , genetics , enzyme , amino acid , population , chemistry , biology , microbiology and biotechnology , biochemistry , gene , missense mutation , medicine , leucine , environmental health
Maple Syrup Urine Disease is a rare metabolic disorder caused by reduced/absent activity of the branched chain α‐Ketoacid dehydrogenase enzyme complex. Mutations in BCKDHA , BCKDHB , and DBT , that encode important subunits of the enzyme complex namely E1α, E1β, 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 E1α or E1β 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: 3122–3132, 2012. © 2012 Wiley Periodicals, Inc.