title: A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain.
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 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.
authors.affiliation: Universitat Autònoma de Barcelona and the Hospital Meterno-Infantil Vall d'Hebron, Barcelona, Spain.
authors.forename: Elsa
authors.initials: E
authors.lastname: Callén
authors.forename: José A
authors.initials: JA
authors.lastname: Casado
authors.forename: Marc D
authors.initials: MD
authors.lastname: Tischkowitz
authors.forename: Juan A
authors.initials: JA
authors.lastname: Bueren
authors.forename: Amadeu
authors.initials: A
authors.lastname: Creus
authors.forename: Ricard
authors.initials: R
authors.lastname: Marcos
authors.forename: Angeles
authors.initials: A
authors.lastname: Dasí
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Estella
authors.forename: Arturo
authors.initials: A
authors.lastname: Muñoz
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Ortega
authors.forename: Johan
authors.initials: J
authors.lastname: de Winter
authors.forename: Hans
authors.initials: H
authors.lastname: Joenje
authors.forename: Detlev
authors.initials: D
authors.lastname: Schindler
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.forename: Shirley V
authors.initials: SV
authors.lastname: Hodgson
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Mathew
authors.forename: Jordi
authors.initials: J
authors.lastname: Surrallés
mesh_terms: D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005192:Family Health; D005199:Fanconi Anemia / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D052217:Fanconi Anemia Complementation Group A Protein; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D017354:Point Mutation; D015995:Prevalence; D013030:Spain / Q000208:ethnology
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein