Two novel translocation breakpoints upstream of SOX9 define borders of the proximal and distal breakpoint cluster region in campomelic dysplasia
Two novel translocation breakpoints upstream of SOX9 define borders of the proximal and distal breakpoint cluster region in campomelic dysplasia
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DOI：
10.1111/j.1399-0004.2007.00736.x
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发表时间：
2007-01-01
影响因子：
3.5
通讯作者：
Scherer, G.
中科院分区：
文献类型：
--
作者：
Leipoldt, M.;Erdel, M.;Scherer, G.
半致死性骨骼畸形综合征伴或不伴XY性逆转的肢端发育不良（CD）是由17q24.3上的SOX 9基因内的突变或具有SOX 9编码区外的断点的染色体畸变（易位、倒位或缺失）引起的。先前发表的SOX 9上游的CD易位断裂点分为两个簇：断裂点在50-300 kb之间的近端簇和断裂点在899-932 kb之间的远端簇。在这里，我们提出的临床，细胞遗传学和分子数据从两个新的CD易位的情况下。例1染色体核型为46，XY，t（1;17）（q42.1;q24.3），具有CD的特征性症状，包括轻度胫骨弓曲、隐睾和尿道下裂。通过标准荧光原位杂交（FISH）和高分辨率的光纤FISH，17 q断裂点被定位在距离SOX 9 375 kb处，定义了近端断裂点簇区域的着丝粒边界。例2核型为46，X，t（Y;17）（q11.2;q24.3），为CD缺肢型，XY完全性逆转。通过FISH和体细胞杂交分析，17 q断裂点定位在SOX 9的789 kb处，定义了远端断裂点簇区域的端粒边界。我们讨论了1 Mb顺式控制区上游的SOX 9和14映射易位断点的位置与疾病的严重程度和XY性逆转之间的相关性的结构。
The semilethal skeletal malformation syndrome campomelic dysplasia (CD) with or without XY sex reversal is caused by mutations within the SOX9 gene on 17q24.3 or by chromosomal aberrations (translocations, inversions or deletions) with breakpoints outside the SOX9 coding region. The previously published CD translocation breakpoints upstream of SOX9 fall into two clusters: a proximal cluster with breakpoints between 50-300 kb and a distal cluster with breakpoints between 899-932 kb. Here, we present clinical, cytogenetic and molecular data from two novel CD translocation cases. Case 1 with karyotype 46,XY,t(1;17)(q42.1;q24.3) has characteristic symptoms of CD, including mild tibial bowing, cryptorchidism and hypospadias. By standard fluorescence in situ hybridization (FISH) and by high-resolution fiber FISH, the 17q breakpoint was mapped 375 kb from SOX9, defining the centromeric border of the proximal breakpoint cluster region. Case 2 with karyotype 46,X,t(Y;17)(q11.2;q24.3) has the acampomelic form of CD and complete XY sex reversal. By FISH and somatic cell hybrid analysis, the 17q breakpoint was mapped 789 kb from SOX9, defining the telomeric border of the distal breakpoint cluster region. We discuss the structure of the 1 Mb cis-control region upstream of SOX9 and the correlation between the position of the 14 mapped translocation breakpoints with respect to disease severity and XY sex reversal.