Novel Founder Mutation in FANCA Gene (c.3446_3449dupCCCT) Among Romani Patients from the Balkan Region

Abstract

Background: Fanconi anemia is a rare autosomalrecessive or X-linked disorder characterised by clinicaland genetic heterogeneity. Most fanconi anemiapatients harbour homozygous or double heterozygousmutations in the FANCA (60-65%), FANCC (10-15%), FANCG (~10%) or FANCD2 (3-6%) genes.We have already reported the FANCA variant c.190–256_283+1680del2040dupC as a founder mutationamong Macedonian fanconi anemia patients of Gypsylikeethnic origin. Here, we present a novel FANCAmutation in two patients from Macedonia and Kosovo.Case Report: The novel FANCA mutationc.3446_3449dupCCCT was identified in twofanconi anemia patients with Romany ethnicity; a2-year-old girl from Macedonia who is a compoundheterozygote for a previously reported FANCA c.190-256_283+1680del2040dupC and the novel mutation anda 10-year-old girl from Kosovo who is a homozygotefor the novel FANCA c.3446_3449dupCCCT mutation.The novel mutation is located in exon 35 in the FAAP20-binding domain which plays a crucial role in the FANCAFAAP20interaction and is required for integrity of thefanconi anemia pathway.Conclusion: The finding of the FANCAc.3446_3449dupCCCT mutation in two unrelated FApatients with Romani ethnicity from Macedonia andKosovo suggests it is a founder mutation in the Romanipopulation living in the Balkan region.