NROB1 duplication-associated DSD

Deletion of the dosage sensitive gene NR0B1 encoding DAX1 on chromosome Xp21.2 results in congenital adrenal hypoplasia (AHC), whereas NR0B1 duplication in 46,XY individuals leads to gonadal dysgenesis and a female phenotype.

Synopsis

 DAX1 duplication-associated DSD

• Xp21.2 interstitial duplication containing the DAX1 gene
• DAX1 duplications at Xp11.2 (17504899)
• Functional disomy of Xp by t(X;Y)(p21.2;p11.3) (15216557)
  • Translocations involving the short arms of the X and Y in human chromosomes are uncommon.
  • One of the best-known consequences of such exchanges is sex reversal in 46,XX males and some 46,XY females, due to exchange in the paternal germline of terminal portions of Xp and Yp, including the SRY gene.
  • Translocations of Xp segments to the Y chromosome result in functional disomy of the X chromosome with an abnormal phenotype and sex reversal if the DSS locus, mapped in Xp21, is present. (15216557)

See also

 NR0B1 (DAX1, AHCH) at Xp21.3

References

 Gene dosage imbalances in patients with 46,XY gonadal DSD detected by an in-house-designed synthetic probe set for multiplex ligation-dependent probe amplification analysis. Barbaro M, Cicognani A, Balsamo A, Löfgren A, Baldazzi L, Wedell A, Oscarson M. Clin Genet. 2008 May;73(5):453-64. PMID: 18384427

 Mutations in the SRY, DAX1, SF1 and WNT4 genes in Brazilian sex-reversed patients. Domenice S, Corrêa RV, Costa EM, Nishi MY, Vilain E, Arnhold IJ, Mendonca BB. Braz J Med Biol Res. 2004 Jan;37(1):145-50. PMID: 14689056

 Isolated 46,XY gonadal dysgenesis in two sisters caused by a Xp21.2 interstitial duplication containing the DAX1 gene. Barbaro M, Oscarson M, Schoumans J, Staaf J, Ivarsson SA, Wedell A. J Clin Endocrinol Metab. 2007 Aug;92(8):3305-13. PMID: 17504899 (Free)

 Functional disomy of Xp including duplication of DAX1 gene with sex reversal due to t(X;Y)(p21.2;p11.3). Sanlaville D, Vialard F, Thépot F, Vue-Droy L, Ardalan A, Nizard P, Corré A, Devauchelle B, Martin-Denavit T, Nouchy M, Malan V, Taillemite JL, Portnoï MF. Am J Med Genet A. 2004 Jul 30;128A(3):325-30. PMID: 15216557