title: Isodicentric Y chromosomes in Egyptian patients with disorders of sex development (DSD).
abstract: Isodicentric chromosome formation is the most common structural abnormality of the Y chromosome. As dicentrics are mitotically unstable, they are subsequently lost during cell division resulting in mosaicism with a 45,X cell line. We report on six patients with variable signs of disorders of sex development (DSD) including ambiguous genitalia, short stature, primary amenorrhea, and male infertility with azoospermia. Cytogenetic studies showed the presence of a sex chromosome marker in all patients; associated with a 45,X cell line in five of them. Fluorescence in situ hybridization (FISH) technique was used to determine the structure and the breakage sites of the markers that all proved to be isodicentric Y chromosomes. Three patients, were found to have similar breakpoints: idic Y(qter→ p11.32:: p11.32→ qter), two of them presented with ambiguous genitalia and were found to have ovotesticular DSD, while the third presented with short stature and hypomelanosis of Ito. One female patient presenting with primary amenorrhea, Turner manifestations and ambiguous genitalia revealed the breakpoint: idic Y (pter→q11.1::q11.1→pter). The same breakpoint was detected in a male with azoospermia but in non-mosaic form. An infant with ambiguous genitalia and mixed gonadal dysgenesis (MGD) had the breakpoint at Yq11.2: idic Y(pter→q11.2::q11.2→pter). SRY signals were detected in all patients. Sequencing of the SRY gene was carried out for three patients with normal results. This study emphasizes the importance of FISH analysis in the diagnosis of patients with DSD as well as the establishment of the relationship between phenotype and karyotype.
authors.affiliation: Division of Human Genetics and Genomic Research, Department of Human Cytogenetics, National Research Center, 33 El-Behouth st., Dokki, 12311, Cairo, Egypt. monamekkawy2005@yahoo.com
authors.forename: Mona
authors.initials: M
authors.lastname: Mekkawy
authors.forename: Alaa
authors.initials: A
authors.lastname: Kamel
authors.forename: Mona
authors.initials: M
authors.lastname: El-Ruby
authors.forename: Amal
authors.initials: A
authors.lastname: Mohamed
authors.forename: Mona
authors.initials: M
authors.lastname: Essawi
authors.forename: Hala
authors.initials: H
authors.lastname: Soliman
authors.forename: Nabil
authors.initials: N
authors.lastname: Dessouky
authors.forename: Marwa
authors.initials: M
authors.lastname: Shehab
authors.forename: Inas
authors.initials: I
authors.lastname: Mazen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D041322:Chromosomes, Human, Y; D012734:Disorders of Sex Development / Q000175:diagnosis / Q000235:genetics*; D004534:Egypt; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D059785:Karyotype; D008297:Male; D010641:Phenotype; D012729:Sex Chromosome Aberrations; D055815:Young Adult