Molecular and structural analyses of maple syrup urine disease and identification of a founder mutation in a Portuguese Gypsy community

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Sofia Quental (Author) Other; Sandra Macedo Ribeiro (Author) Other; Raquel Matos (Author) Other; Laura Vilarinho (Author) Other; Esmeralda Martins (Author) Other; Elisa Leao Teles (Author) Other; Esmeralda Rodrigues (Author) Other; Luisa Diogo (Author) Other; Paula Garcia (Author) Other; Filomena Eusebio (Author) Other; Ana Gaspar (Author) Other; Silvia Sequeira (Author) Other; Fatima Furtado (Author) Other; Isabel Lanca (Author) Other; Antonio Amorim (Author) FCUP; Maria Joao Prata (Author) FCUP

Journal

Title: Molecular Genetics and Metabolism

Vol. 94

Pages: 148-156

ISSN: 1096-7192

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 25 Citations

Scopus - 29 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-003-Z4D

DOI: 10.1016/j.ymgme.2008.02.008

Abstract (EN): Maple syrup urine disease (MSUD) is an autosomal recessive disorder, caused by the defective function of the branched-chain alpha-ketoacid dehydrogenase complex (BCKD). BCKD is a mitochondrial complex, encoded by four nuclear genes (BCKDHA, BCKDHB, DBT and DLD), involved in the metabolism of branched-chain amino acids (BCAAs). Since the MSUD mutational spectrum has not been previously assessed in Portugal, in this study we present the molecular characterization of 30 MSUD Portuguese patients. Seventeen putative mutations have been identified (six in BCKDHA, five in BCKDHB and six in DBT); seven of them are here described for the first time. The most common mutation identified was a C deletion in BCKDHA gene (c.117delC; p.R40GfsX23), already reported in the Spanish population. Interestingly, it was found in all patients of a Gypsy community from South of the country, so a founder effect is probably responsible for the high incidence of the disease in this community. Structural models of MSUD missense mutations have been performed to understand their pathogenic effect, in order to elucidate and often to predict the severity of a mutation clinical consequence.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9