Revisiting MSUD in Portuguese Gypsies: Evidence for a Founder Mutation and for a Mutational Hotspot within the BCKDHA Gene

• Tipo: Artigo em Revista Científica Internacional
• Data: 2009

Autores

Sofia Quental (Autor) Outra; Alfredo Gusmao (Autor) Outra; Pilar Rodriguez Pombo (Autor) Outra; Magdalena Ugarte (Autor) Outra; Laura Vilarinho (Autor) Outra; Antonio Amorim (Autor) FCUP; Maria J Prata (Autor) FCUP

Revista

Título: Annals of Human Genetics

Vol. 73

Páginas: 298-303

ISSN: 0003-4800

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 10 Citações

Scopus - 10 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências da terra e ciências do ambiente

Outras Informações

ID Authenticus: P-003-K6D

DOI: 10.1111/j.1469-1809.2009.00518.x

Abstract (EN): Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder of branched-chain amino acid metabolism. In the context of the wide mutational spectrum known for this disease, a few common mutations have been described in populations where founder effects played a major role in modeling diversities. In Portugal, for instance, a high proportion of patients are of Gypsy origin and all share the same mutation (c.117delC-alpha; p.R40GfsX23), causing the neonatal severe form of MSUD. In this study, we used four microsatellite markers closely flanking the BCKDHA gene (E1 alpha protein) to demonstrate that c.117delC-alpha is a founder mutation responsible for the high incidence of the disorder among Portuguese Gypsies. These results are of medical relevance since carrier tests and prenatal diagnosis can be offered to families at risk, particularly because the carrier frequency of c.117delC-alpha was estimated at 1.4% among the healthy Portuguese Gypsies from the South of the country. Finally we present evidence that the genomic region of the BCKDHA gene where c.117delC-alpha is located is likely a mutational hotspot, since recurrence of c.117delC-alpha was observed in two distinct population groups.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6