Identification and molecular cytogenetic characterization of a novel complex Y chromosome rearrangement in a boy with disorder of sexual development

• Published in: Gene 2013-05, Vol.519 (2), p.374-380
• Main Authors: Dutta, Usha R., Pidugu, Vijaya Kumar, Goud, Ch. Venkateshwar, Hoefers, Christiane, Hagemann, Monika, Dalal, Ashwin
• Format: Article
• Language: English
• Subjects: Ambiguous genitalia; bacterial artificial chromosomes; boys; Centromere - genetics; centromeres; Child; Chromosome Disorders - genetics; Chromosome Disorders - metabolism; chromosome translocation; Chromosomes, Human, Pair 15 - genetics; Chromosomes, Human, Y - genetics; clones; congenital abnormalities; cytogenetic analysis; Cytogenetic Analysis - methods; Deletion; Derivative chromosome; Disorders of Sex Development - genetics; Disorders of Sex Development - pathology; DNA; DNA Probes - genetics; Duplication; FISH; fluorescence in situ hybridization; Gene Deletion; Gene Dosage; Gene Rearrangement; Genes, Duplicate; genitalia; Humans; In Situ Hybridization, Fluorescence; Male; patients; quantitative polymerase chain reaction; Real-Time Polymerase Chain Reaction; Sex Chromosome Aberrations; sexual development; Translocation; Translocation, Genetic; Y chromosome
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2013.01.065

Ambiguous genitalia or disorder of the sexual development is a birth defect where the external genitals do not have the typical appearance of either a male or female. Here we report a boy with ambiguous genitalia and short stature. The cytogenetic analysis by G-banding revealed a small Y chromosome and an additional material on the 15p arm. Further, molecular cytogenetic analysis by Fluorescence in situ hybridization (FISH) using whole chromosome paint probes showed the presence of Y sequences on the 15p arm, confirming that it is a Y;15 translocation. Subsequent, FISH with centromere probe Y showed two signals depicting the presence of two centromeres and differing with a balanced translocation. The dicentric nature of the derivative 15 chromosome was confirmed by FISH with both 15 and Y centromeric probes. Further, the delineation of the Y chromosomal DNA was also done by quantitative real time PCR. Additional Y-short tandem repeat typing was performed to find out the extent of deletion on small Y chromosome. Fine mapping was carried out with 8 Y specific BAC clones which helped in defining the breakpoint regions. MLPA was performed to check the presence or absence of subtelomeric regions and SHOX regions on Y. Finally array CGH helped us in confirming the breakpoint regions. In our study we identified and characterized a novel complex Y chromosomal rearrangement with a complete deletion of the Yq region and duplication of the Yp region with one copy being translocated onto the15p arm. This is the first report of novel and unique Y complex rearrangement showing a deletion, duplication and a translocation in the same patient. The possible mechanism of the rearrangement and the phenotype–genotype correlation are discussed. [Display omitted] ► Complex Y; Autosomal rearrangement associated with disorder of sexual development. ► Novel Y chromosomal rearrangement; Yq deletion, Yp duplication copy on 15p region. ► Unique Y chromosome rearrangement showing deletion, duplication and translocation.