Bessant D A, Payne A M, Plant C, Bird A C, Bhattacharya S S
Department of Molecular Genetics, Institute of Ophthalmology, University College London, UK.
J Med Genet. 1998 Sep;35(9):773-4. doi: 10.1136/jmg.35.9.773.
Usher syndrome (USH) is characterised by congenital sensorineural hearing loss and progressive pigmentary retinopathy. All three subtypes (USH1, USH2, and USH3) are inherited as recessive traits. People with Usher type 2 (USH2) have normal vestibular responses and moderate to severe hearing loss. These syndromes have been found to be genetically heterogeneous, with a single locus for USH2 at 1q41 (USH2A), six loci for USH1, and one for USH3. Some USH2 families have been excluded from the 1q41 locus suggesting that a second, as yet unidentified, locus (USH2B) must exist. Linkage studies suggest that around 90% of USH2 families are USH2A. Four USH2 families were analysed for linkage to markers flanking the USH2A locus. In one of these families a recombination event was observed in an affected subject which excludes the USH2A gene from proximal to the marker AFM143XF10 and defines this as the new centromeric flanking marker for the USH2A locus. A further recombination event in another patient from this family confirmed AFM144XF2 as the telomeric flanking marker. The interval between these polymorphic markers is estimated to be 400 kb. This region is completely contained in each of three YACs from the CEPH library: 867g9, 919h3, and 848b9. This refinement more than halves the critical genetic interval and will greatly facilitate positional cloning of the USH2A gene.
尤塞氏综合征（USH）的特征是先天性感音神经性听力损失和进行性色素性视网膜病变。所有三种亚型（USH1、USH2和USH3）均以隐性性状遗传。患有2型尤塞氏综合征（USH2）的人前庭反应正常，听力损失为中度至重度。已发现这些综合征在遗传上具有异质性，USH2在1q41有一个基因座（USH2A），USH1有六个基因座，USH3有一个基因座。一些USH2家族已被排除在1q41基因座之外，这表明第二个尚未确定的基因座（USH2B）必定存在。连锁研究表明，约90%的USH2家族是USH2A。对四个USH2家族进行了与USH2A基因座侧翼标记的连锁分析。在其中一个家族中，在一名受影响的个体中观察到一次重组事件，该事件将USH2A基因从标记AFM143XF10近端排除，并将其定义为USH2A基因座的新着丝粒侧翼标记。来自该家族的另一名患者的另一次重组事件证实AFM144XF2为端粒侧翼标记。这些多态性标记之间的间隔估计为400 kb。该区域完全包含在来自CEPH文库的三个酵母人工染色体（YAC）中：867g9、919h3和848b9。这种细化使关键遗传间隔减半以上，并将极大地促进USH2A基因的定位克隆。
