Clinical and cytogenetic variability on twelve Fanconi anemia families andits relationship with complementation group assignment

Objective. To describe the clinical and cytogenetic features of Mexican pat ients with Fanconi anemia, while assessing whether the phenotypic variation is related to the complementation group. Material and methods. The cytogen etic diagnosis was done using mitomycin C and diepoxybutane on peripheral b lood lymphocytes. The severity of the anemia and each patient's clinical ma nifestations were classified using Alter's and Auerbach's clinical scores, respectively. Lymphoblastoid cell lines were established for eight patients and complementation group determined following cell fusion procedures in f our propositi. Results. Twenty-five Fanconi anemia patients from 12 familie s were studied. All patients had high, spontaneous and induced chromosomal breakages, no relationship was found between the clinical severity of the d isease and the anemic state. Twelve patients were considered severely ill, while the remaining 13 were considered mild cases. Three individuals were a nemia-free, while in 13 the anemia was mild, moderate in 7, and severe in 1 . The mortality rate was 32% (8/25). No relationship was found between the clinical picture and degree of the anemia or mortality rate. Eleven patient s were assigned to complementation group A with mild clinical findings and anemia. Their cytogenetic results showed variability. One patient assigned to group C was considered as a severe case with transfusion-dependent anemi a and high sensitivity to mutagens. Thirteen patients were not classified. A lymphoblastoid cell line resistant to mitomycin C was obtained suggesting somatic mosaicism. Conclusions. The establishment of a complementation gro up does not necessarily explain variability. There are other important fact ors, such as somatic mosaicism, that modify the cellular phenotype.