Clinical, genetic and cytogenetic study of Fanconi anemia in an Indian population

Abstract

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.

Características clínicas de pacientes com anemia de Fanconi

“…Although craniofacial abnormalities are subtle, some authors claim that they might enable the clinical identification of individuals with FA (25) . Skin abnormalities, in turn, are described in the literature in 45-60% of cases, and are characterized mainly, as observed in our sample, by café au lait spots and localized or usually generalized hyperpigmentation (2,23) .…”

“…These figures are considered to be triradial when there are two breakages and tetraradial when there are three breakages. In the study of karyotype, the number, the type and the distribution of the chromosome breakages are detected in each cell (2,10,(20)(21)(22)(23) . The degree of sensitivity to DEB or MMC is not correlated with neither the phenotype nor the severity of the disease.…”

How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel

“…FA is a mostly autosomal recessive [Auerbach, 2009; de Winter and Joenje, 2009] DNA repair syndrome [D'Andrea, 2010] associated with progressive pancytopenia, acute myeloid leukemia, and specific solid tumors [Alter, 2003a,b]. Notably high carrier frequencies have been estimated for several founder populations [Rosendorff et al, 1987; Tipping et al, 2001; Callen et al, 2005; Morgan et al, 2005], and FA occurs worldwide [Macdougall et al, 1994; Altay et al, 1997; Tamary et al, 2000; Xie et al, 2001; Bouchlaka et al, 2003; Yagasaki et al, 2003; Magdalena et al, 2005; Tootian et al, 2006; Korgaonkar et al, 2010], but carrier frequencies in different countries remain unknown.…”

Untitled

“…This is comparable to that reported from Korea 11 but half the rate reported from India. 9 Leukemia as an initial presentation was present in 5% of the study population. This is double the rate reported in the International Fanconi Anemia Registry Study.…”