Molecular genetic analysis of MSUD from India reveals mutations causing altered protein truncation affecting the C-termini of E1α and E1ß.
J Cell Biochem
; 113(10): 3122-32, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-22593002
ABSTRACT
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, E1ß, 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 E1ß 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mutación Missense
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3-Metil-2-Oxobutanoato Deshidrogenasa (Lipoamida)
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Enfermedad de la Orina de Jarabe de Arce
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Complejos Multienzimáticos
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Female
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Humans
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Infant
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Male
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Newborn
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Cell Biochem
Año:
2012
Tipo del documento:
Article
País de afiliación:
India