Clinical, genetic and cytogenetic study of Fanconi anemia in an Indian population.
Fanconi anemia (FA) is a rare autosomal recessive genetic disease, associated with congenital anomalies and a predisposition to cancers. FA patients exhibit spontaneous chromosome breakage and FA cells are sensitive to DNA interstrand crosslink agents and expresses high frequency of chromosome breakage. Recently 13 genes have been shown to be involved with the FA phenotype. We have carried out a detailed study in clinically diagnosed FA patients in an Indian population. Thirty three patients were clinically diagnosed with FA and had aplastic anemia and bleeding abnormalities. The genetic analysis revealed a significantly (P<0.0001) high frequency (36.4%) of parental consanguinity in FA patients compared to controls (3.33%). Chromosomal analysis revealed spontaneous chromosome breakage in 63.64% FA patients. The mitomycin C and diepoxybutane induced cultures showed a significantly (P<0.001) high frequency of chromosome breakage and radial formation compared to controls. Among 33 patients, nine (27.27%) patients developed malignancies and chromosomal abnormalities were detected in five (55.5%) patients bone marrow cells including monosomy 5 and 7, trisomy 10, der(1q) and inv(7). Cytogenetic investigation is important in aplastic anemia to rule out FA. The clinical presentation and the associated high frequency of consanguinity in FA, and the molecular analysis are complementary in the study of an Indian population.
Department of Cytogenetics, National Institute of Immunohaematology, Parel, Mumbai, India.
Seema
S
Korgaonkar
Kanjaksha
K
Ghosh
Babu Rao
BR
Vundinti
D000293:Adolescent; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage / Q000187:drug effects; D002873:Chromosome Fragility / Q000235:genetics; D002877:Chromosomes, Human / Q000187:drug effects; D003241:Consanguinity; D004852:Epoxy Compounds / Q000494:pharmacology; D005199:Fanconi Anemia / Q000097:blood / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000235:genetics; D008297:Male; D016685:Mitomycin / Q000494:pharmacology; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000235:genetics; D055815:Young Adult
D004852:Epoxy Compounds; D016685:Mitomycin; C007366:diepoxybutane