A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain

Elsa Callén, José A. Casado, Marc D. Tischkowitz, Juan A. Bueren, Amadeu Creus, Ricard Marcos, Angeles Dasí, Jesús M. Estella, Arturo Muñoz, Juan J. Ortega, Johan De Winter, Hans Joenje, Detlev Schindler, Helmut Hanenberg, Shirley V. Hodgson, Christopher G. Mathew, Jordi Surrallés

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Abstract

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 muta tion 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.

Original languageEnglish (US)
Pages (from-to)1946-1949
Number of pages4
JournalBlood
Volume105
Issue number5
DOIs
StatePublished - Mar 1 2005

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Callén, E., Casado, J. A., Tischkowitz, M. D., Bueren, J. A., Creus, A., Marcos, R., Dasí, A., Estella, J. M., Muñoz, A., Ortega, J. J., De Winter, J., Joenje, H., Schindler, D., Hanenberg, H., Hodgson, S. V., Mathew, C. G., & Surrallés, J. (2005). A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain. Blood, 105(5), 1946-1949. https://doi.org/10.1182/blood-2004-07-2588