RESUMO
Fanconi anemia (FA) is an autosomal recessive disorder associated with hypersensitivity to DNA cross-linking agents and bone marrow failure. At least four complementation groups have been defined, and the FA group C gene (FAC) has been cloned. We have screened 76 unrelated FA patients of diverse ethnic and geographic origins and from unknown complementation groups for mutations in the FAC gene either by chemical cleavage mismatch analysis or by single-strand conformational polymorphism (SSCP). Five mutations were detected in four patients (5.3%), including two novel mutations (W22X and L496R). Nine polymorphisms were detected, seven of which have not been described previously (663A-->G, L190F, IVS6 + 30C-->T, I312V, V449M, Q465R, and 1974G-->A). Six of the nine polymorphisms occurred in patients or controls from the Tswana or Sotho chiefdoms of South Africa and were not found in 50 unrelated European controls. Restriction site assays were established for all 8 pathogenic mutations identified in the FAC gene to date and used to screen a total of 94 unrelated FA patients. This identified only one other group C patient, who was homozygons for the mutation IVS4 + 4A-->T. This study indicates that the proportion of FA patients from complementation group C is generally likely to be less than 10%. Guidelines for the selection of FA patients for FAC mutation screening are proposed.
Assuntos
Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Anemia de Fanconi/genética , Mutação , Proteínas Nucleares , Polimorfismo Genético , Proteínas/genética , Proteína do Grupo de Complementação C da Anemia de Fanconi , Proteínas de Grupos de Complementação da Anemia de Fanconi , Heterozigoto , Homozigoto , Humanos , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita SimplesRESUMO
The cytogenetics of cell cultures derived from Dupuytren's tissue, adjacent palmar fascia and palmar skin from patients undergoing fasciectomy have been examined and the results compared to cell cultures established from palmar fascia, flexor retinaculum and palmar skin of patients undergoing carpal tunnel decompression. Chromosomal abnormalities were detected in cell cultures from Dupuytren's tissue in eight of the nine patients studied. Clones of cells trisomic for chromosome 8 were found in five of the nine patients. Trisomy 8 was also present in two of five flexor retinaculum cultures from carpal tunnel syndrome cases. These findings in both Dupuytren's contracture and carpal tunnel syndrome suggest the presence of chromosomal instability in the palmar fascia. The significance of the chromosomal abnormalities is however unclear, but they indicate a possible common pathway in the onset of pathological fibrosis.
Assuntos
Síndrome do Túnel Carpal/genética , Cromossomos Humanos Par 8 , Contratura de Dupuytren/genética , Trissomia , Adulto , Idoso , Células Clonais/ultraestrutura , Fáscia/ultraestrutura , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Pele/ultraestruturaRESUMO
Diabetes insipidus (DI) is a rare complication of acute myelogenous leukemia (AML). Five of the six such cases described in the literature who had banded chromosomal studies performed had monosomy 7 and the sixth patient had del(7)(q22). A further case of AML complicated by DI in whom banded chromosomal studies revealed a complex karyotypic abnormality, including monosomy 7, is reported. The association between monosomy 7 and DI in AML appears specific but the reason for this association remains unclear.