BACKGROUND/ PURPOSE: XX male is a rare sex chromosomal disorder in infertile men. The purpose of this study was to distinguish the clinical and genetic features of the 46,XX male syndrome from other more frequent, testicular-origin azoospermic causes of male infertility. METHODS: To study 46,XX male syndrome, we compared clinical and endocrinological parameters to other groups with testicular-origin azoospermia, and to an age-matched group of healthy males and females as normal control. Fluorescent in situ hybridization for detection and localization of the sex-determining region of the Y gene (SRY), array-based comparative genomic hybridization screening, and real-time qualitative polymerase chain reaction of FGF9, WT1, NR5A1, and SPRY2 genes were performed in this genetic investigation. RESULTS: Our three patients with 46,XX male syndrome had a much higher follicular-stimulating hormone level, lower body height, lower testosterone level, and ambiguous external genitalia. One of the three patients with 46,XX male syndrome was SRY-negative. A further genetic study, including a comparative genomic hybridization array and real-time polymerase chain reaction, showed a gain of FGF9 copy numbers only in the SRY-negative 46,XX male. The genetic copy number of the FGF9 gene was duplicated in that case compared to the normal female control and was significantly lower than that of the normal male control. No such genomic gain was observed in the case of the two SRY-positive 46,XX males. CONCLUSION: Similar to clinical manifestations of 46,XX male syndrome, genetic evidence in this study suggests that FGF9 may contribute to sex reversal, but additional confirmation with more cases is still needed.
BACKGROUND/ PURPOSE: XX male is a rare sex chromosomal disorder in infertilemen. The purpose of this study was to distinguish the clinical and genetic features of the 46,XX male syndrome from other more frequent, testicular-origin azoospermic causes of male infertility. METHODS: To study 46,XX male syndrome, we compared clinical and endocrinological parameters to other groups with testicular-origin azoospermia, and to an age-matched group of healthy males and females as normal control. Fluorescent in situ hybridization for detection and localization of the sex-determining region of the Y gene (SRY), array-based comparative genomic hybridization screening, and real-time qualitative polymerase chain reaction of FGF9, WT1, NR5A1, and SPRY2 genes were performed in this genetic investigation. RESULTS: Our three patients with 46,XX male syndrome had a much higher follicular-stimulating hormone level, lower body height, lower testosterone level, and ambiguous external genitalia. One of the three patients with 46,XX male syndrome was SRY-negative. A further genetic study, including a comparative genomic hybridization array and real-time polymerase chain reaction, showed a gain of FGF9 copy numbers only in the SRY-negative 46,XX male. The genetic copy number of the FGF9 gene was duplicated in that case compared to the normal female control and was significantly lower than that of the normal male control. No such genomic gain was observed in the case of the two SRY-positive 46,XX males. CONCLUSION: Similar to clinical manifestations of 46,XX male syndrome, genetic evidence in this study suggests that FGF9 may contribute to sex reversal, but additional confirmation with more cases is still needed.
Authors: Stefanie Eggers; Simon Sadedin; Jocelyn A van den Bergen; Gorjana Robevska; Thomas Ohnesorg; Jacqueline Hewitt; Luke Lambeth; Aurore Bouty; Ingrid M Knarston; Tiong Yang Tan; Fergus Cameron; George Werther; John Hutson; Michele O'Connell; Sonia R Grover; Yves Heloury; Margaret Zacharin; Philip Bergman; Chris Kimber; Justin Brown; Nathalie Webb; Matthew F Hunter; Shubha Srinivasan; Angela Titmuss; Charles F Verge; David Mowat; Grahame Smith; Janine Smith; Lisa Ewans; Carolyn Shalhoub; Patricia Crock; Chris Cowell; Gary M Leong; Makato Ono; Antony R Lafferty; Tony Huynh; Uma Visser; Catherine S Choong; Fiona McKenzie; Nicholas Pachter; Elizabeth M Thompson; Jennifer Couper; Anne Baxendale; Jozef Gecz; Benjamin J Wheeler; Craig Jefferies; Karen MacKenzie; Paul Hofman; Philippa Carter; Richard I King; Csilla Krausz; Conny M A van Ravenswaaij-Arts; Leendert Looijenga; Sten Drop; Stefan Riedl; Martine Cools; Angelika Dawson; Achmad Zulfa Juniarto; Vaman Khadilkar; Anuradha Khadilkar; Vijayalakshmi Bhatia; Vũ Chí Dũng; Irum Atta; Jamal Raza; Nguyen Thi Diem Chi; Tran Kiem Hao; Vincent Harley; Peter Koopman; Garry Warne; Sultana Faradz; Alicia Oshlack; Katie L Ayers; Andrew H Sinclair Journal: Genome Biol Date: 2016-11-29 Impact factor: 13.583
Authors: Ahmad Majzoub; Mohamed Arafa; Christopher Starks; Haitham Elbardisi; Sami Al Said; Edmund Sabanegh Journal: Asian J Androl Date: 2017 Mar-Apr Impact factor: 3.285