title: Fanconi anemia founder mutation in Macedonian patients.
abstract: BACKGROUND
  Fanconi anemia (FA) is a rare autosomal recessive disorder clinically characterized by developmental abnormalities, progressive bone marrow failure (BMF) and profound cancer predisposition. Approximately 65% of all affected individuals have mutation in the FANCA (Fanconi anemia complementation group A) gene. The mutation spectrum of the FANCA gene is highly heterogeneous. FA-A is usually associated with private FANCA mutations in individual families.
  
  
  METHODS
  We describe 3 unrelated patients with FA with a similar clinical presentation: BMF, renal anomalies and café-au-lait pigmentation without major skeletal abnormality. The molecular analysis of the FANCA gene using the FA MLPA kit P031-A2/P032 FANCA, showed homozygous deletion of exon 3 in all 3 patients. Molecular analysis of the flanking regions of exon 3 precisely defined unique deletion of 2,040 bp and duplication of C (1788_3828dupC).
  
  
  CONCLUSIONS
  These are the first 3 patients homozygous for deletion of FANCA exon 3 described to date. Although not related, the patients originated from the same Gypsy-like ethnic population. We conclude that c.190-256_283 + 1680del2040 dupC mutation in the FANCA gene is a founder mutation in Macedonian FA patients of Gypsy-like ethnic origin. Our finding has very strong implications for these patients in formulating diagnostic and carrier-screening strategy for BMF and FA and to enable comprehensive genetic counseling.
authors.affiliation: Research Center for Genetic Engineering and Biotechnology 'Georgi D. Efremov', Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Madjunkova
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Kocheva
authors.forename: Dijana
authors.initials: D
authors.lastname: Plaseska-Karanfilska
mesh_terms: D000293:Adolescent; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons; D005199:Fanconi Anemia / Q000235:genetics*; D052217:Fanconi Anemia Complementation Group A Protein / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D018843:Republic of North Macedonia; D006178:Romani People / Q000235:genetics; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein