de Kok Y J, Merkx G F, van der Maarel S M, Huber I, Malcolm S, Ropers H H, Cremers F P
Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
Hum Mol Genet. 1995 Nov;4(11):2145-50. doi: 10.1093/hmg/4.11.2145.
X-linked deafness with stapes fixation (DFN3) is caused by mutations in the POU3F4 gene at Xq21.1. By employing pulsed field gel electrophoresis (PFGE) we identified a chromosomal aberration in the DNA of a DFN3 patient who did not show alterations in the open reading frame (ORF) of POU3F4. Southern blot analysis indicated that a DNA segment of 150 kb, located 170 kb proximal to the POU3F4 gene, was duplicated. Fluorescence in situ hybridization (FISH) analysis, PFGE, and detailed Southern analysis revealed that this duplication is part of a more complex rearrangement including a paracentric inversion involving the Xq21.1 region, and presumably the Xq21.3 region. Since at least two DFN3-associated minideletions are situated proximal to the duplicated segment, the inversion most likely disconnects the POU3F4 gene from a regulatory element which is located at a distance of at least 400 kb upstream of the POU3F4 gene.
伴有镫骨固定的X连锁耳聋（DFN3）由位于Xq21.1的POU3F4基因突变引起。通过采用脉冲场凝胶电泳（PFGE），我们在一名DFN3患者的DNA中鉴定出一种染色体畸变，该患者的POU3F4开放阅读框（ORF）未显示出改变。Southern印迹分析表明，位于POU3F4基因近端170 kb处的一个150 kb的DNA片段发生了重复。荧光原位杂交（FISH）分析、PFGE和详细的Southern分析显示，这种重复是一个更复杂重排的一部分，该重排包括涉及Xq21.1区域以及可能的Xq21.3区域的臂间倒位。由于至少两个与DFN3相关的微小缺失位于重复片段的近端，因此该倒位很可能使POU3F4基因与一个位于POU3F4基因上游至少400 kb处的调控元件断开连接。
