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Medline ® Abstract for Reference 27

of 'Clinical manifestations and diagnosis of Fanconi anemia'

27
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A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain.
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Callén E, Casado JA, Tischkowitz MD, Bueren JA, Creus A, Marcos R, DasíA, Estella JM, Muñoz A, Ortega JJ, de Winter J, Joenje H, Schindler D, Hanenberg H, Hodgson SV, Mathew CG, Surrallés J
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Blood. 2005 Mar;105(5):1946-9. Epub 2004 November 2.
 
Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure and cancer predisposition. Here we have identified Spanish Gypsies as the ethnic group with the world's highest prevalence of FA (carrier frequency of 1/64-1/70). DNA sequencing of the FANCA gene in 8 unrelated Spanish Gypsy FA families after retroviral subtyping revealed a homozygous FANCA mutation (295C>T) leading to FANCA truncation and FA pathway disruption. This mutation appeared specific for Spanish Gypsies as it is not found in other Gypsy patients with FA from Hungary, Germany, Slovakia, and Ireland. Haplotype analysis showed that Spanish Gypsy patients all share the same haplotype. Our data thus suggest that the high incidence of FA among Spanish Gypsies is due to an ancestral founder mutation in FANCA that originated in Spain less than 600 years ago. The high carrier frequency makes the Spanish Gypsies a population model to study FA heterozygote mutations in cancer.
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Universitat Autònoma de Barcelona and the Hospital Meterno-Infantil Vall d'Hebron, Barcelona, Spain.
PMID