Haplotype analysis suggests a single Balkan origin for the Gaucher disease [D409H;H255Q] double mutant allele

Gaucher disease is an autosomal recessive lysosomal storage disease that is mainly due to mutations in the GBA gene. Most of the mutant alleles described so far bear a single mutation. However, there are a few alleles bearing two or more DNA changes. It has been reported that patients homozygous for...

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Published in:Human mutation Vol. 29; no. 6; pp. E58 - E67
Main Authors: Santamaria, Raül, Michelakakis, Helen, Moraitou, Marina, Dimitriou, Evangelia, Dominissini, Silvia, Grossi, Serena, Sánchez-Ollé, Gessamí, Chabás, Amparo, Pittis, María Gabriela, Filocamo, Mirella, Vilageliu, Lluïsa, Grinberg, Daniel
Format: Journal Article
Language:English
Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-06-2008
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Summary:Gaucher disease is an autosomal recessive lysosomal storage disease that is mainly due to mutations in the GBA gene. Most of the mutant alleles described so far bear a single mutation. However, there are a few alleles bearing two or more DNA changes. It has been reported that patients homozygous for the [D409H;H255Q] double mutant allele (HGVS-approved nomenclature, p.[D448H;H294Q]) present a more severe phenotype than patients homozygous for the relatively common D409H mutation. In this study, we confirmed the detrimental cumulative effect of these two mutations at the enzymatic activity level by the heterologous expression of the single and double mutant alleles. Additionally, we found a high frequency of the [D409H;H255Q] allele in patients from the Balkans and the Adriatic area of Italy. This prompted us to perform a haplotype analysis, using five microsatellite polymorphisms close to the GBA gene, to determine the origin of this allele. The results of the 37 chromosomes analysed showed that most of them share a common haplotype and are consistent with a single origin in the Balkans and the Adriatic area of Italy for the [D409H;H255Q] allele.
Bibliography:http://dx.doi.org/10.1002/humu.20776
Communicated by Elizabeth F. Neufeld
ark:/67375/WNG-1VCWQSPX-H
istex:37CF556B9702011382497F5C2AE3CA34E7D336A1
Spanish Ministerio de Educación y Ciencia, Spanish FIS and Catalan AGAUR - No. SAF2006-12276; No. PI042350; No. 2005SGR00848
ArticleID:HUMU20776
These authors contributed equally to this work.
ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1059-7794
1098-1004
DOI:10.1002/humu.20776