Ebermann Inga, Wilke Robert, Lauhoff Thomas, Lübben Dirk, Zrenner Eberhart, Bolz Hanno Jörn
Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany.
Mol Vis. 2007 Aug 30;13:1539-47.
To identify the genetic defect in a German family with Usher syndrome (USH) and linkage to the USH3A locus.
DNA samples of five family members (both parents and the three patients) were genotyped with polymorphic microsatellite markers specific for eight USH genes. Three affected family members underwent detailed ocular and audiologic characterization.
Symptoms in the patients were compatible with Usher syndrome and show intrafamilial variation, for both hearing loss (ranging from severe to profound with non-linear progression) and vision. Genotyping of microsatellite markers for the different USH loci was in line with a defect in the USH3A gene on chromosome 3q25. Sequence analysis of the USH3A gene revealed two truncating mutations; c.149_152delCAGGinsTGTCCAAT, which has been described previously, and a novel mutation, c.502_503insA, segregating with the phenotype.
To date, only 11 USH3A mutations have been described. This is the first description of a German family with USH due to USH3A mutations, including one novel. Our findings indicate that also in the Central European population, USH3A mutations should be considered in cases of USH.
确定一个患有Usher综合征（USH）的德国家庭的基因缺陷，并将其与USH3A基因座进行连锁分析。
使用针对八个USH基因的多态性微卫星标记对五名家庭成员（父母双方和三名患者）的DNA样本进行基因分型。对三名受影响的家庭成员进行了详细的眼部和听力特征分析。
患者的症状与Usher综合征相符，并且在听力损失（从重度到极重度，呈非线性进展）和视力方面均表现出家族内差异。对不同USH基因座的微卫星标记进行基因分型，结果与3号染色体q25上的USH3A基因缺陷一致。对USH3A基因进行序列分析，发现了两个截短突变；c.149_152delCAGGinsTGTCCAAT（此前已有描述）和一个新突变c.502_503insA，该突变与表型共分离。
迄今为止，仅描述了11种USH3A突变。这是首次对一个因USH3A突变导致USH的德国家庭进行描述，其中包括一种新突变。我们的研究结果表明，在中欧人群中，对于USH病例也应考虑USH3A突变。
