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

• Type: Article in International Scientific Journal
• Date: 2009

Authors

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

Journal

Title: Annals of Human Genetics

Vol. 73

Pages: 298-303

ISSN: 0003-4800

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 10 Citations

Scientific classification

FOS: Natural sciences > Earth and related Environmental sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6