46,XY Disorder of Sex Development

Duplications of the NR0B1 gene and the surrounding genomic region, referred to as the dosage-sensitive sex reversal (DSS) region, do not cause X-linked AHC but instead result in a 46,XY disorder of sex development. Although most patients reported with duplications of the DSS region have complete gonadal dysgenesis causing XY sex reversal, partial gonadal dysgenesis with ambiguous genitalia has been described (Barbaro et al., 2008). Duplications of DAX1 in 46,XX individuals have no known clinical consequence, but the risk of transmission to 46,XY offspring is a significant consideration.

Tests Available

Forms and Documents

Test Details

NR0B1
  • To determine the etiology of primary adrenal insufficiency in a male, particularly in the presence of HH, an X-linked family history, and/or symptoms suggestive of a contiguous gene deletion syndrome
  • To determine etiology of 46,XY gonadal dysgenesis and ambiguous genitalia
  • Carrier testing for females with a family history of X-linked AHC
  • Prenatal diagnosis for at-risk pregnancies
  • Capillary Sequencing

Ordering

416
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Dried Blood Spots | Buccal Swabs

Billing

81404x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Morel et al., (January 2010) Studies of a cohort of 46,XY with DSD including steroid biosynthesis deficiencies Presented at Hormonal and Genetic Basis of Sexual Differentiation Disorder and Hot Topics in Endocrinology, Miami, FL
  2. Bardoni et al., (1994) Nat Genet 7:497-501
  3. Salvi et al., (2002) J Clin Endocrinol Metab 87:4094-4100
  4. Lin et al., (2006) J Clin Endocrinol Metab 91:3048-3054
  5. Muscatelli et al., (1994) Nature 372:672-676
  6. McCabe ERB (2007) Mol Cell Endocrinol 265- 266:179-182
  7. Ho et al., (2004) Mol Genet Metab 83:330-336
  8. Zhang et al., (1998) Am J Hum Genet 62:855-864
  9. Barbaro et al., (2008) Clin Genet 73:453-464
  10. Shaikh et al., (2008) J Med Genet 45:e1
  11. Seminara et al., (1999) J Clin Endocrinol Metab 84:4501- 4509
  12. Merke et al., (1999) NEJM 340:1248-1252
  13. Mantovani et al., (2002) J Clin Endocrinol Metab 87:44-48
  14. Achermann et al., (2001) Molec Cell Endocrinol 185:17-25

Forms and Documents

Test Details

CHD7, CYP19A1, DUSP6, ESR1, FEZF1, FGF17, FGF8, FGFR1, GNRH1, GNRHR, HS6ST1, IL17RD, KAL1, KISS1, KISS1R, LEP, LEPR, LHB, LHCGR, NR0B1, NR5A1, NSMF, POLR3B, PROK2, PROKR2, PROP1, SEMA3A, SEMA3E, SOX10, SPRY4, TAC3, TACR3, WDR11
  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management of individuals with HH
  • Testing of at-risk relatives for specific known mutation(s) previously identified in an affected family member
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Next-Gen Sequencing
  • Deletion/Duplication Analysis

Ordering

676
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81404x2, 81406x2, 81407x1, 81479x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Balasubramanian R, Crowley WF Jr. Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency. 2007 May 23 [Updated 2017 Mar 2]. In: Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993
  2. Brioude et al., (2010) Eur J Endocrinol 162:835-851 (PMID: 20207726)
  3. Kim et al., (2008) Am J Hum Genet 83(4):511-519 (PMID: 18834967)
  4. Dubern et al., (2012) Biochimie 94 (10): 2111-2115 (PMID: 22627381)
  5. Faroqui et al., (2007) The New England Journal Of Medicine 356 (3):237-247 (PMID: 17229951)
  6. Arnhold et al., (2009) Horm. Res. 71: 75-82 (PMID: 19129711)
  7. Raivio et al., (2007) N Engl J Med 357(9):863-873 (PMID: 17761590)
  8. Silveira et al., (2010) Mol Cell Endocrinol 324(1-2):30-38 (PMID: 20188792)
  9. Luo et al. (2015) Gynecol Endocrinol 31(7): 516-521 (PMID:26036718)
  10. Leschek et al., (2001) J. Pediat. 138: 949-951 (PMID: 11391350)
  11. Quaynor et al., (2011) Fertil Steril 96(6): 1424-1430 (PMID: 22035731)
  12. Bianco & Kaiser, (2009) Nat Rev Endocrinol 5(10):569-576 (PMID: 19707180)