Sankila E M, Pakarinen L, Kääriäinen H, Aittomäki K, Karjalainen S, Sistonen P, de la Chapelle A
Department of Medical Genetics, University of Helsinki, Finland.
Hum Mol Genet. 1995 Jan;4(1):93-8. doi: 10.1093/hmg/4.1.93.
Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Type I (USH1) is characterized by a congenital, severe to profound hearing loss and absent vestibular function; in type II (USH2) the hearing loss is congenital and moderate to severe, and the vestibular function is normal. Progressive pigmentary retinopathy (PPR) is present in both types. A third type (USH3) differing from USH2 by the progressive nature of its hearing loss has been suggested. USH3 has previously been estimated to comprise 2% of all USH. However, based on clinical criteria, in Finland 42% of USH patients have progressive hearing loss suggesting enrichment of an USH3 gene. We excluded the four previously mapped USH regions as the site of the USH3 disease locus. Systematic search for USH3 by genetic linkage analyses in 10 multiple affected families using polymorphic microsatellite markers revealed significant linkage with markers mapping to chromosome 3q. Pairwise lod scores at zero recombination distance were 7.87 for D3S1308, and 11.29 for D3S1299, incorporating the observed linkage disequilibrium. Conventional multipoint linkage analysis gave a maximum lod score of 9.88 at D3S1299 assigning USH3 to the 5 cM interval between markers D3S1555 and D3S1279 in 3q21-25.(ABSTRACT TRUNCATED AT 250 WORDS)
尤塞氏综合征（USH）指的是具有视觉和听力联合丧失症状的遗传性和临床异质性常染色体隐性疾病。I型（USH1）的特征是先天性重度至极重度听力丧失且前庭功能缺失；II型（USH2）的听力丧失是先天性的，为中度至重度，前庭功能正常。两种类型均存在进行性色素性视网膜病变（PPR）。有人提出了第三种类型（USH3），其听力丧失具有进行性，与USH2不同。USH3此前估计占所有USH病例的2%。然而，根据临床标准，在芬兰，42%的USH患者有进行性听力丧失，提示USH3基因富集。我们排除了先前定位的四个USH区域作为USH3疾病基因座的位点。使用多态性微卫星标记对10个多病例家庭进行遗传连锁分析，系统地寻找USH3，结果显示与定位于3号染色体q臂的标记有显著连锁。考虑到观察到的连锁不平衡，在零重组距离处，D3S1308的成对连锁分数为7.87，D3S1299的成对连锁分数为11.29。传统的多点连锁分析在D3S1299处给出的最大连锁分数为9.88，将USH3定位于3q21 - 25区域中标记D3S1555和D3S1279之间5厘摩的区间内。（摘要截短于250字）
