De Novo 12;17 Translocation Upstream of SOX9 Resulting in 46,XX Testicular Disorder of Sex Development

被引:27
作者
Refai, Osama [1 ]
Friedman, Andrew [1 ]
Terry, Lori [2 ]
Jewett, Tamison [2 ]
Pearlman, Alexander [1 ]
Perle, Mary Ann [3 ]
Ostrer, Harry [1 ]
机构
[1] NYU, Sch Med, Human Genet Program, Dept Pediat, New York, NY 10016 USA
[2] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA
[3] NYU, Sch Med, Dept Pathol, Cytogenet Lab, New York, NY 10016 USA
关键词
sex determination; 12:17 translocation; SOX9; 46; XX testicular DSD; arrayCGH analysis; FISH; SRY-RELATED GENE; CAMPOMELIC DYSPLASIA; REVERSAL; REGION; BREAKPOINTS; DIFFERENTIATION; DOWNSTREAM; MUTATIONS; DELETION; MALES;
D O I
10.1002/ajmg.a.33201
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Individuals with rare cytogenetic variants have contributed to our understanding of the genetics of sex development and its disorders. Here, we report on a child with a de novo 12;17 translocation, 46,XX,t(12;17)(q14.3;q24.3) chromosome complement, resulting in SRY-negative 46,XX testicular disorder of sex development (46,XX DSD without campomelic dysplasia). The chromosome 12 breakpoint was mapped via array comparative genomic hybridization (aCGH) of a hybrid somatic cell line to 64.2-64.6 Mb (from the p arm telomere). The chromosome 17 breakpoint was mapped to 66.4-67.1 Mb, that is, upstream of SOX9. The location of the chromosome 17 breakpoint was refined by fluorescence in situ hybridization (FISH) at >= 776kb upstream of SOX9. Thus, the 12;17 translocation removed part of the SOX9 cis-regulatory region and replaced it with a regulatory element from pseudogene LOC204010 or the next gene, Deynar, of chromosome 12, potentially causing upregulation of the testis-determining SOX9 gene during gonadal development and the phenotype of 46,XX testicular DSD. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:422 / 426
页数:5
相关论文
共 25 条
[1]   Long-range upstream and downstream enhancers control distinct subsets of the complex spatiotemporal Sox9 expression pattern [J].
Bagheri-Fam, S ;
Barrionuevo, F ;
Dohrmann, U ;
Günther, T ;
Schüle, R ;
Kemler, R ;
Mallo, M ;
Kanzler, B ;
Scherer, G .
DEVELOPMENTAL BIOLOGY, 2006, 291 (02) :382-397
[2]  
de la Chapelle A, 1990, Reprod Nutr Dev, VSuppl 1, p39s
[3]   THE ROLE OF THE SEX-DETERMINING REGION-Y GENE IN THE ETIOLOGY OF 46,XX MALENESS [J].
FECHNER, PY ;
MARCANTONIO, SM ;
JASWANEY, V ;
STETTEN, G ;
GOODFELLOW, PN ;
MIGEON, CJ ;
SMITH, KD ;
BERKOVITZ, GD ;
AMRHEIN, JA ;
BARD, PA ;
LEE, PA ;
REID, C ;
TSALIKIAN, E ;
URBAN, MD .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1993, 76 (03) :690-695
[4]   CAMPOMELIC DYSPLASIA AND AUTOSOMAL SEX REVERSAL CAUSED BY MUTATIONS IN AN SRY-RELATED GENE [J].
FOSTER, JW ;
DOMINGUEZSTEGLICH, MA ;
GUIOLI, S ;
KWOK, C ;
WELLER, PA ;
STEVANOVIC, M ;
WEISSENBACH, J ;
MANSOUR, S ;
YOUNG, ID ;
GOODFELLOW, PN ;
BROOK, JD ;
SCHAFER, AJ .
NATURE, 1994, 372 (6506) :525-530
[5]  
Huang B, 1999, AM J MED GENET, V87, P349, DOI 10.1002/(SICI)1096-8628(19991203)87:4<349::AID-AJMG13>3.0.CO
[6]  
2-N
[7]  
Hughes IA, 2006, ARCH DIS CHILD, V91, P554, DOI [10.1136/adc.2006.098319, 10.1016/j.jpurol.2006.03.004]
[8]   Up-regulation of SOX9 in human sex-determining region on the Y chromosome (SRY)-negative XX males [J].
Kojima, Yoshiyuki ;
Hayashi, Yutaro ;
Mizuno, Kentaro ;
Sasaki, Shoichi ;
Fukui, Yuko ;
Koopman, Peter ;
Morohashi, Ken-Ichiro ;
Kohri, Kenjiro .
CLINICAL ENDOCRINOLOGY, 2008, 68 (05) :791-799
[9]   Two novel translocation breakpoints upstream of SOX9 define borders of the proximal and distal breakpoint cluster region in campomelic dysplasia [J].
Leipoldt, M. ;
Erdel, M. ;
Bien-Willner, G. A. ;
Smyk, M. ;
Theurl, M. ;
Yatsenko, S. A. ;
Lupski, J. R. ;
Lane, A. H. ;
Shanske, A. L. ;
Stankiewicz, P. ;
Scherer, G. .
CLINICAL GENETICS, 2007, 71 (01) :67-75
[10]   Sex determination: a 'window' of DAX1 activity [J].
Ludbrook, LM ;
Harley, VR .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2004, 15 (03) :116-121