A NEW X-LINKED RECESSIVE DEAFNESS SYNDROME WITH BLINDNESS, DYSTONIA, FRACTURES, AND MENTAL DEFICIENCY IS LINKED TO XQ22
A NEW X-LINKED RECESSIVE DEAFNESS SYNDROME WITH BLINDNESS, DYSTONIA, FRACTURES, AND MENTAL DEFICIENCY IS LINKED TO XQ22
复制标题
DOI：
10.1136/jmg.32.4.257
复制
发表时间：
1995-04-01
影响因子：
4
通讯作者：
LUBS, H
中科院分区：
文献类型：
--
作者：
TRANEBJAERG, L;SCHWARTZ, C;LUBS, H
X连锁隐性耳聋仅占所有儿童耳聋的1.7%。在至少28种不同的与听力障碍相关的X连锁综合征中，只有少数在分子水平上得到了表征。1960年，一个挪威大家庭报告了早发性进行性感音神经性耳聋，在McKusick中索引为DFN-1，McKusick 304700。当时没有相关症状的描述。这个家族已经被重新临床研究。广泛的神经学、神经生理学、神经放射学和生物化学以及分子技术已被应用于诊断X连锁隐性综合征。家族史和广泛的特点，16个受影响的男性在五代证实了X连锁隐性遗传和语后进行性感音神经性耳聋。对原始DFN-1家族的重新研究表明，耳聋是一种进行性X连锁隐性综合征的一部分，该综合征包括导致皮质盲的视力残疾、肌张力障碍、骨折和智力缺陷。连锁分析表明，该基因与Xq 22的DXS 101位点连锁，lod值为5.37（零重组）。基于多点分析的lod-l支持区间，该基因位于该位点近端5cM至远端3cM的区域内。由于蛋白脂质蛋白基因（PLP）位于该区域内，并且突变已被证明与非经典PMD相关。（Pelizaeus-Merzbacher病），如复杂X连锁遗传性痉挛性截瘫，PLP可能代表了这种疾病的候选基因。（Mohr-Tranebjaerg综合征，MTS）并提供了关于一种新的X连锁隐性综合征型耳聋的重要新信息，这种耳聋以前被认为是孤立的耳聋
X linked recessive deafness accounts for only 1.7% of all childhood deafness. Only a few of the at least 28 different X linked syndromes associated with hearing impairment have been characterised at the molecular level. In 1960, a large Norwegian family was reported with early onset progressive sensorineural deafness, which was indexed in McKusick as DFN-1, McKusick 304700. No associated symptoms were described at that time.This family has been restudied clinically. Extensive neurological, neurophysiological, neuroradiological, and biochemical, as well as molecular techniques, have been applied to characterise the X linked recessive syndrome. The family history and extensive characterisation of 16 affected males in five generations confirmed the X linked recessive inheritance and the postlingual progressive nature of the sensorineural deafness. Some obligate carrier females showed signs of minor neuropathy and mild hearing impairment.Restudy of the original DFN-1 family showed that the deafness is part of a progressive X linked recessive syndrome, which includes visual disability leading to cortical blindness, dystonia, fractures, and mental deficiency. Linkage analysis indicated that the gene was Linked to locus DXS101 in Xq22 with a lod score of 5.37 (zero recombination). Based on lod-l support interval of the multipoint analysis, the gene is located in a region spanning from 5 cM proximal to 3 cM distal to this locus. As the proteolipid protein gene (PLP) is within this region and mutations have been shown to be associated with non-classical PMD (Pelizaeus-Merzbacher disease), such as complex X linked hereditary spastic paraplegia, PLP may represent a candidate gene for this disorder.This family represents a new syndrome (Mohr-Tranebjaerg syndrome, MTS) and provides significant new information about a new X Linked recessive syndromic type of deafness which was previously thought to be isolated deafness.