1/2. De novo dup(X)(q22.3q26) in a girl with evidence that functional disomy of X material is the cause of her abnormal phenotype.The relationship between phenotype and Xq duplications in females remains unclear. Some females are normal; some have short stature; and others have features such as microcephaly, developmental delay/mental retardation, body asymmetries, and gonadal dysgenesis. There are several hypotheses proposed in the literature to explain this variability. We describe a 7-year-old girl with dup(X)(q22.3q26). The pregnancy was complicated by intrauterine growth retardation, and she was distressed during labor. During her first year she fed poorly and failed to thrive. She has microcephaly, her height is at the 10th centile, and her hands and feet are strikingly small. She is hypotonic and delayed. Asymmetries of muscle power, and of leg and foot length have been noted. She has mild unilateral ptosis. She has some features of turner syndrome, and multiple other minor anomalies such as flat labia. These are features common to other described females. This report describes our patient in detail and compares her phenotype to those of the other females with Xq duplications, displays our laboratory investigations, and discusses ideas regarding the pathogenesis of phenotype. The duplicated X is of paternal origin. It is inactivated in all cells; however, the distal duplicated portion appears to be active. We suggest that functional disomy of the duplicated X material, due to local escape from inactivation, may be responsible for the phenotype in the affected females.- - - - - - - - - - ranking = 1keywords = gonadal dysgenesis, dysgenesis (Clic here for more details about this article) |
2/2. A 46,X,inv(Y) young woman with gonadal dysgenesis and gonadoblastoma: cytogenetics, molecular, and methylation studies.cytogenetic analysis of a young woman with gonadal dysgenesis and bilateral gonadoblastoma shared a male karyotype with a rearranged y chromosome, interpreted as a pericentric inversion. The breakpoints, defined by fluorescent in situ hybridization (FISH), were located on the very distal short arm on band Yp11.31 and in the middle of the Yq12 long arm heterochromatic region. FISH analysis documented that the short arm breakpoint was 93 Kb distal to SRY and disrupted the CD99 gene, which was transposed to the distal portion of Yq12. The proposita's phenotype was similar to that of XY individuals with gonadal dysgenesis but without signs of Ullrich-turner syndrome. There were no mutations in the SRY gene. cytogenetic analysis in the proposita's father showed mosaicism of a normal y chromosome and several different rearrangements, such as deletion of a heterochromatin portion at band Yq12.2, a fragile site at the same band, structural rearrangements between the Y-chromosome and other autosomes, Y-chromosome aneuploidies, and "Premature centromere Division" (PCD) anomaly. The proposita's inverted y chromosome appears to have originated from paternal y chromosome instability. The patient's female phenotype could be due to SRY CpG methylation-mediated positional effects (PEV).- - - - - - - - - - ranking = 6keywords = gonadal dysgenesis, dysgenesis (Clic here for more details about this article) |