Callén Elsa, Casado José A, Tischkowitz Marc D, Bueren Juan A, Creus Amadeu, Marcos Ricard, Dasí Angeles, Estella Jesús M, Muñoz Arturo, Ortega Juan J, de Winter Johan, Joenje Hans, Schindler Detlev, Hanenberg Helmut, Hodgson Shirley V, Mathew Christopher G, Surrallés Jordi
Universitat Autònoma de Barcelona and the Hospital Meterno-Infantil Vall d'Hebron, Barcelona, Spain.
Blood. 2005 Mar 1;105(5):1946-9. doi: 10.1182/blood-2004-07-2588. Epub 2004 Nov 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.
范可尼贫血（FA）是一种以骨髓衰竭和癌症易感性为特征的遗传性疾病。我们发现西班牙吉普赛人是世界上FA患病率最高的族群（携带者频率为1/64 - 1/70）。对8个不相关的西班牙吉普赛FA家族进行逆转录病毒亚型分析后，对FANCA基因进行DNA测序，发现了一个纯合的FANCA突变（295C>T），导致FANCA截短和FA通路破坏。该突变似乎是西班牙吉普赛人特有的，因为在匈牙利、德国、斯洛伐克和爱尔兰的其他患有FA的吉普赛患者中未发现。单倍型分析表明，西班牙吉普赛患者都共享相同的单倍型。因此，我们的数据表明，西班牙吉普赛人中FA的高发病率是由于FANCA中一个起源于不到600年前西班牙的祖先奠基者突变。高携带者频率使西班牙吉普赛人成为研究癌症中FA杂合子突变的群体模型。
