A new chromosome instability disorder.
Chromosome analysis in a 31-year-old woman referred for primary amenorrhea, revealed a very high incidence of chromosome aberrations. She had microcephaly and immunodeficiency. Her healthy parents were consanguineous (1/32) and a younger sister, also with primary amenorrhea, died when 20 years old with a malignant lymphoma. Chromosome studies were performed on lymphocytes and fibroblasts and in both tissues a high proportion of metaphases with multiple chromosome aberrations was found. Clonal and sporadic rearrangements, consisting of balanced and unbalanced translocations and dicentric chromosomes were more numerous than chromatid and chromosome breaks. In the lymphocytes the same unbalanced translocation t(8q;21q) was present in about 59% of the metaphases. Rearrangements involving chromosomes 7 and 14, similar to those described in patients with ataxia-telangiectasia were found, but with a lower frequency. Sister Chromatid Exchanges were not increased. Chromosome and chromatid abnormalities were enhanced after exposure of cells to mitomycin C but not after exposure to the radiomimetic drug bleomycin. Clinical and cytogenetic characteristics of the patient are compared with those of syndromes (Ataxia-Telangiectasia and Werner's syndrome) or isolated cases (Weemaes et al. 1981, Sperling 1983, Spinner et al. 1985) whose features are similar to those of our patient. This case might represent a new chromosome instability syndrome due to a recessive mutation.
D000328:Adult; D000568:Amenorrhea / Q000235:genetics*; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14; D002891:Chromosomes, Human, Pair 21; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics*; D013577:Syndrome; D014178:Translocation, Genetic