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Analysis of gene mutations among South Indian patients with maple syrup urine disease: Identification of four novel mutations

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Title Analysis of gene mutations among South Indian patients with maple syrup urine disease: Identification of four novel mutations
 
Creator Narayanan, M P
Menon, Krishnakumar N
Vasudevan, D M
 
Subject Maple syrup urine disease
BCKD complex
BCKDHA
BCKDHB
DBT
Mutation analysis
 
Description 442-446
Maple syrup urine disease (MSUD) is
predominantly caused by mutations in the BCKDHA, BCKDHB and DBT genes, which
encode for the E1α, E1β and E2 subunits of the branched-chain α-keto
acid dehydrogenase complex, respectively. Because disease causing mutations
play a major role in the development of the disease, prenatal diagnosis at
gestational level may have significance in making decisions by parents. Thus,
this study was aimed to screen South Indian MSUD patients for mutations and
assess the genotype-phenotype correlation. Thirteen patients diagnosed with
MSUD by conventional biochemical screening such as urine analysis by DNPH test,
thin layer chromatography for amino acids and blood amino acid quantification
by HPLC were selected for mutation analysis. The entire coding regions of the
BCKDHA, BCKDHB and DBT genes were analyzed for mutations by PCR-based direct
DNA sequencing. BCKDHA and BCKDHB mutations were seen in 43% of the total ten
patients, while disease-causing DBT gene mutation was observed only in 14%.
Three patients displayed no mutations. Novel mutations were c.130C>T in
BCKDHA gene, c. 599C>T and c.121_122delAC in BCKDHB gene and c.190G>A in
DBT gene. Notably, patients harbouring these mutations were
non-responsive to thiamine supplementation and other treatment regimens and might
have a worse prognosis as compared to the patients not having such mutations. Thus,
identification of these mutations may have a crucial role in the treatment as
well as understanding the molecular mechanisms in MSUD.
 
Date 2013-10-26T09:52:33Z
2013-10-26T09:52:33Z
2013-10
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/22645
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.50(5) [October 2013]