Haploinsufficiency of the DMRT Gene Cluster in a Case with 46,XY Ovotesticular Disorder of Sexual Development
Haploinsufficiency of the DMRT Gene Cluster in a Case with 46,XY Ovotesticular Disorder of Sexual Development
Background: Ovotesticular disorder is characterized by the presenceof testicular and ovarian tissues in the same individual. Single genemutations in SRY, SOX9, DMRT1 and DAX1 can lead to ovotesticulardisorder of sexual development.Case Report: Herein, we report a 3-month-old phenotypically femalebaby in whom differentiated tissues of both Müllerian and Wolffianducts were detected on pathological analysis of laparoscopic biopsymaterial. Chromosomal analysis observed 46,XY, der(9)t(3;9)(p25;p24) with deletion of 9p24.3p23 including the DMRT genecluster and duplication of 3p26.3p24.3 on array comparative genomichybridisation.Conclusion: In support of previous literature, we found thathaploinsufficiency of the DMRT gene cluster leads to ovotesticulardisorder of sexual development. In addition, we emphasize that arraycomparative genomic hybridisation is an important technique in themolecular diagnosis of ovotesticular disorder of sexual.
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- Reiss JA, Sheffield LJ, Sutherland GR. Partial trisomy 3p syndrome. Clin Genet
1986;30:50-8.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.