Females with gonadal dysgenesis: cytogenetic and molecular analysis

ABSTRACT

Gonadal dysgenesis [GD] is a congenital defect in gonadal development related to abnormalities of genes controlling sexual differentiation and includes a wide spectrum of patients with variable phenotypes and chromosomal constitutions. This study aimed at studying the spectrum of chromosomal abnormalities as related to the phenotypic variability of GD cases and to detect the presence of Y-ctiromosome specific sequences in these patients by using molecular techniques in order to allow, early prophylactic management. Seventy females presenting with female GD were referred to the Human genetic clinic, National Research Center for cytogenetic analysis and genetic counseling. Patients were subjected to clinical examination, pedigree construction, cytogenetic and molecular analysis. Hormonal studies, pelvic ultrasonogrophy, Laparoscopy and gonadal biopsy were performed whenever possible. Patients were classified according to their Karyotypes into 9 groups. The most frequent Karyotype, was 45, X [34.3%]. The association of 45, X with other cell lines were found at a rate of 28.6%. The age of studied cases ranged between 15 days to 31.07 years [mean=140.9 years]. The total parental consanguinity rate reached 44.3%. Gonadal dysgenesis and short stature are the two cardinal signs in these patients. Skeletal features were detected among all studied groups with highest scores in patients having complete X monosomy [44.6%]. Neck webbing was a characteristic sign of patients with non-mosaic 45, X karyotype. Dysmorphic features were detected in all groups with the exception of groups with 46, XX and 46, XY Karyotypes. Hirsutism and other virilizing signs were not commonly detected among the studied cases. Gonadoblastoma was detected in only one case among the 5 cases examined by Laparoscopic biopsy. Unidentified sex chromosomes markers constituted 35% of all our 45, X mosaic patterns. Molecular analysis of the markers using PCR technique proved the presence of Y specific sequences, SRY, in three cases. The over all rate of Y chromosomal material detected among these patients either by cytogenetic or molecular methods was 14, 3%