9p Partial Monosomy and Disorders of Sex Development: Review and Postulation of a Pathogenetic Mechanism

被引:22
作者
Quinonez, Shane C. [1 ]
Park, John M. [2 ]
Rabah, Raja [3 ]
Owens, Kailey M. [1 ]
Yashar, Beverly M. [4 ]
Glover, Thomas W. [1 ,4 ]
Keegan, Catherine E. [1 ,4 ]
机构
[1] Univ Michigan, Dept Pediat, Div Genet, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
关键词
distal monosomy 9p; 9p partial monosomy; disorders of sexual development; gonadoblastoma; 46; XY GONADAL-DYSGENESIS; CONGENITAL HEART-DEFECTS; HUMAN-CHROMOSOME; 9P; DELETION; PARTIAL TRISOMY; SHORT ARM; TESTIS DEVELOPMENT; XY FEMALES; DISTAL; REVERSAL;
D O I
10.1002/ajmg.a.36018
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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. DMR . 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. (C) 2013 Wiley Periodicals, Inc.
引用
收藏
页码:1882 / 1896
页数:15
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