Fanconi anemia and its diagnosis

Abstract

Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia, and predisposition to both hematologic malignancies and solid tumors. Congenital anomalies vary from patient to patient and may affect skeletal morphogenesis as well as any of the major organ systems. Although this highly variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, laboratory study of chromosomal breakage induced by diepoxybutane (DEB) or other crosslinking agents provides a unique cellular marker for the diagnosis of the disorder either prenatally or postnatally. Diagnosis based on abnormal response to DNA crosslinking agents can be used to identify the pre-anemia patient as well as patients with aplastic anemia or leukemia who may or may not have the physical stigmata associated with the syndrome. This overview will present our present knowledge regarding the varied phenotypic manifestations of FA and procedures for diagnosis based upon abnormal DNA damage responses.

Características clínicas de pacientes com anemia de Fanconi

“…The method was based on the technique described by Auerbach et al (16) in 1981, in which cultures of lymphocytes stimulated with phytohemagglutinin of patients and controls (matched for age and sex) were exposed to DEB. In the analysis of the results, we considered the mean chromosome breakage identified by metaphase analyzed both in basal cultures (without DEB) and in those using this alkylating agent, and the number of cells with radial figures.…”

Diagnosis of acquired aplastic anemia

“…A normal clinical examination does not definitively rule out a 'cryptic' dyskeratosis congenita 16,17 or a non-classical Fanconi anemia. 18 The presence of unusual clinical features should alert the possibility of a congenital form of AA. Peripheral blood lymphocytes should be tested for spontaneous and diepoxybutane or mitomycin C-induced chromosomal breakage to identify or exclude Fanconi anemia.…”

Phenotypic consequences in black South African Fanconi anemia patients homozygous for a founder mutation

“…7 Worldwide, as documented in the International Fanconi Anemia Registry, FANC A, C, and G mutations are the most prevalent, accounting for 60, 16, and 10% of cases, respectively. 8 In South Africa, black individuals with FA share a common causative founder mutation (637_643delTACCGCC) in the FANCG gene with 80% of cases being homozygous for this mutation. Haplotype analysis of the FANCG gene is consistent with a single origin for this mutation, predating the arrival of Bantu speakers in Southern Africa, in ~400 AD.…”