Haploinsufficiency of the DMRT Gene Cluster in a Case with 46,XY Ovotesticular Disorder of Sexual Development

Year 2018, Volume: 35 Issue: 3, 272 - 274, 01.05.2018

Metin Eser Akif Ayaz

Abstract

Ovotesticular disorder is an extremely rare cause of disorder of sexual development, once known as true hermaphroditism. Herein, we report a 3-month-old phenotypically female baby in whom differentiated tissues of both Müllerian and Wolffian ducts were detected on pathological analysis of laparoscopic biopsy material. Chromosomal analysis observed 46,XY, der(9)t(3;9)(p25;p24) with deletion of 9p24.3p23 including the DMRT gene cluster and duplication of 3p26.3p24.3 on array comparative genomic hybridisation. Background: Ovotesticular disorder is characterized by the presence of testicular and ovarian tissues in the same individual. Single gene mutations in SRY, SOX9, DMRT1 and DAX1 can lead to ovotesticular disorder of sexual development.Case Report: Herein, we report a 3-month-old phenotypically female baby in whom differentiated tissues of both Müllerian and Wolffian ducts were detected on pathological analysis of laparoscopic biopsy material. Chromosomal analysis observed 46,XY, der(9)t(3;9)(p25;p24) with deletion of 9p24.3p23 including the DMRT gene cluster and duplication of 3p26.3p24.3 on array comparative genomic hybridisation.Conclusion: In support of previous literature, we found that haploinsufficiency of the DMRT gene cluster leads to ovotesticular disorder of sexual development. In addition, we emphasize that array comparative genomic hybridisation is an important technique in the molecular diagnosis of ovotesticular disorder of sexual.

Keywords

Genetic hybridization, haploinsufficiency, ovotesticular disorder of sex development

References

• 1. Hughes IA, Houk C, Ahmed SF, Lee PA; Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus Group. Consensus statement on management of intersex disorders. J Pediatr Urol 2006;2:148-62.
• 2. Achermann JC, Hughes IA. Disorders of sex development. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, editors. William’s Textbook of Endocrinology, 12th ed. Saunders: Philadelphia; 2012:887-91.
• 3. Maier EM, Leitner C, Löhrs U, Kuhnle U. True hermaphroditism in an XY individual due to a familial point mutation of the SRY gene. J Pediatr Endocrinol Metab 2003;16:575-80.
• 4. Cameron FJ, Hageman RM, Cooke-Yarborough C, Kwok C, Goodwin LL, Sillence DO, et al. A novel germ line mutation in SOX9 causes familial campomelic dysplasia and sex reversal. Hum Mol Genet 1996;5:1625-30.
• 5. Ledig S, Hiort O, Wünsch L, Wieacker P. Partial deletion of DMRT1 causes 46,XY ovotesticular disorder of sexual development. Eur J Endocrinol 2012;167:119-24.
• 6. Matsui F, Shimada K, Matsumoto F, Itesako T, Nara K, Ida S, et al. Long-term outcome of ovotesticular disorder of sex development: a single center experience. Int J Urol 2011;18:231-6.
• 7. Ludbrook LM, Bernard P, Bagheri-Fam S, Ryan J, Sekido R, Wilhelm D, et al. Excess DAX1 leads to XY ovotesticular disorder of sex development (DSD) in mice by inhibiting steroidogenic factor-1 (SF1) activation of the testis enhancer of SRY-box-9 (SOX9). Endocrinology 2012;153:1948-58.
• 8. Tannour-Louet M, Han S, Corbett ST, Louet JF, Yatsenko S, Meyers L, et al. Identification of de novo copy number variants associated with human disorders of sexual development. PLoS One 2010;5:e15392.
• 9. Erdman SE, Chen HJ, Burtis KC. Functional and genetic characterization of the oligomerization and DNA binding properties of the Drosophila doublesex proteins. Genetics 1996;144:1639-52.
• 10. Raymond CS, Murphy MW, O’Sullivan MG, Bardwell VJ, ZarkowerD. DMRT1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev 2000;14:2587-95.
• 11. Conte RA, Pitter JH, Verma RS. Molecular characterization of trisomic segment 3p24.1-->3pter: a case with review of the literature. Clin Genet 1995;48:49-53.
• 12. Reiss JA, Sheffield LJ, Sutherland GR. Partial trisomy 3p syndrome. Clin Genet 1986;30:50-8.