Phenotypic variability in patients with isodicentric Y(p11.3). a clinical, cytogenetic and molecular study

Abstract

Introduction: Isodicentric (idic) chromosomes are the most common Y structural abnormalities and their influence on gonadal and somatic development is extremely variable. The prediction of their phenotypic consequences is often difficult because of the variety of genomic sequences concerned by duplications and deletions, and the variable degrees of mosaicism, 45, X cell line in particular, in various tissues. The Aim: This study was conducted to provide more information on patients with idic (Yq) allowing a better phenotype-karyotype correlation and understanding the sexual differentiation in these patients . Patients and Methods: The study included 14 patients referred to the out patient
clinic of the Human Genetics Department, Medical Research Institute,University of Alexandria. The reason for referral was genital ambiguity [8 patients], short stature with variable Turner stigmata [4 patients] and primary amenorrhea with normal height [2 patients]. All patients were subjected to clinical examination and chromosome analysis by GTG and CTG-banding techniques. Fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR)were done to determine the structure of the marker chromosomes detected by conventional methods. Results: Chromosome analysis revealed a 45, X/46, X,idic (Y) (p11.3) in ten patients with variable degree of mosaicism, non mosaic 46, X, idic (Y) (p11.3) in two patients and a predominant 46, XX cell line along with 47, XX, idic (Y) (p11.3) cell line in two other patients .While the patients with an idic (Yq) described in this report were phenotypically different, all are considered as being at increased risk for gonadoblastoma. The great phenotypic variations seen in patients with an isodicentric Y
chromosome greatly limit the genotype – phenotype correlation.

Keywords: Isodicentric Y, mosaicism, FISH, SRY, phenotype genotype correlation

Egyptian Journal of Medical Human Genetics Vol. 9 (2) 2008: pp. 189-200