Conflict of interest: none.
9p partial monosomy and disorders of sex development: Review and postulation of a pathogenetic mechanism
Article first published online: 3 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 8, pages 1882–1896, August 2013
How to Cite
2013. 9p partial monosomy and disorders of sex development: Review and postulation of a pathogenetic mechanism. Am J Med Genet Part A. 161A:1882–1896., , , , , , .
- Issue published online: 24 JUL 2013
- Article first published online: 3 JUL 2013
- Manuscript Accepted: 27 MAR 2013
- Manuscript Received: 18 JAN 2013
- distal monosomy 9p;
- 9p partial monosomy;
- disorders of sexual development;
Deletion of the distal segment of 9p causes a syndrome comprising trigonocephaly, minor anomalies, and intellectual disability. Patients with this condition also frequently present with genitourinary abnormalities including cryptorchidism, hypospadias, ambiguous genitalia, or 46,XY testicular dysgenesis. The region responsible for the gonadal dysgenesis has been localized to 9p24.3 with the likely responsible gene identified as DMRT1. Similar to patients with other molecular causes of 46,XY gonadal dysgenesis, patients with partial del 9p have an increased risk of gonadoblastoma. We present two patients with 46,XY gonadal dysgenesis due to partial 9p monosomy. Both patients were also diagnosed with gonadoblastoma following gonadectomy at an early age. Chromosomal microarray analyses refined the cytogenetic abnormalities and allowed potential genotype–phenotype relationships to be determined. We also review the literature as it pertains to partial 9p monosomy, genital abnormalities and gonadoblastoma and note that a large percentage of affected patients present with two copy number variations. We propose that a two-hit mechanism may be involved in the incomplete penetrance and variable expressivity of partial 9p monosomy and an abnormal genital phenotype. The significant percentage of gonadoblastoma in patients with 46,XY complete gonadal dysgenesis due to partial 9p monosomy also continues to support the necessity of gonadectomy in this patient population. © 2013 Wiley Periodicals, Inc.