Identification of a hot spot for microdeletions in patients with X-linked deafness type 3 (DFN3) 900 kb proximal to the DFN3 gene POU3F4
Identification of a hot spot for microdeletions in patients with X-linked deafness type 3 (DFN3) 900 kb proximal to the DFN3 gene POU3F4
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DOI：
10.1093/hmg/5.9.1229
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发表时间：
1996-09-01
影响因子：
3.5
通讯作者：
Cremers, FPM
中科院分区：
文献类型：
--
作者：
deKok, YJM;Vossenaar, ER;Cremers, FPM
最近发现 POU 结构域基因 POU3F4 的小突变可导致 9 名无关男性的 X 连锁耳聋 3 型 (DFN3)。发现 POU3F4 基因位于与 DFN3 相关的五个缺失中的四个之外。其中两个缺失位于 POU3F4 附近 400 kb 以上。通过对该区域的序列标记位点进行 PCR 分析，我们最初在两名 DFN3 患者中发现了新的缺失。为了更详细地研究该染色体片段，我们将先前建立的 850 kb 粘粒重叠群在着丝粒方向上延伸至总大小 1500 kb。来自该重叠群的粘粒与 11 个具有 DFN3 的不相关雄性的 DNA 杂交。在两名患者中，我们发现了包含 POU3F4 基因和不同大小的 Xq21.1 片段的缺失。其余 9 名缺乏 POU3F4 基因突变的患者中，有 6 名患者发现了较小的缺失，除一名例外外，这些缺失在靠近 POU3F4 基因 900 kb 的 8 kb 片段中重叠。在一名患者中，我们在 8 kb DNA 片段附近发现了几个小缺失。缺失总共占所有已知 DFN3 突变的 56% (13/23)，其中大多数 (10/13) 不包含 POU3F4 基因。组合的分子数据表明，Xq21.1 中的缺失热点区域包含另一个 DFN3 基因，或者，一个参与 POU3F4 转录调控的序列元件。
Small mutations in the POU domain gene POU3F4 were recently shown to cause X-linked deafness type 3 (DFN3) in nine unrelated males. The POU3F4 gene was found to be located outside four of five deletions associated with DFN3. Two of these deletions were situated more than 400 kb proximal to POU3F4. Employing PCR analysis of sequence tagged sites from this region we initially identified novel deletions in two DFN3 patients. To investigate this chromosomal segment in more detail, we extended a previously established 850 kb cosmid contig in the centromeric direction to a total size of 1500 kb. Cosmids from this contig were hybridized to DNA of 11 unrelated males with DFN3. In two patients, we identified deletions encompassing the POU3F4 gene and variably sized segments of Xq21.1. In six of the nine remaining patients which lacked mutations in the POU3F4 gene, smaller deletions were identified which, with one exception, overlap in a 8 kb segment 900 kb proximal to the POU3F4 gene. In one patient, we identified several small deletions in the vicinity of the 8 kb DNA segment. Together, deletions account for 56% (13/23) of all known DFN3 mutations, most (10/13) of which do not encompass the POU3F4 gene. The combined molecular data suggest that the deletion hot spot region in Xq21.1 contains another DFN3 gene or, alternatively, a sequence element involved in transcriptional regulation of POU3F4.