Ohata T, Koizumi A, Kayo T, Shoji Y, Watanabe A, Monoh K, Higashi K, Ito S, Ogawa O, Wada Y, Takada G
Department of Hygiene, Akita University School of Medicine, Japan.
Hum Genet. 1998 Oct;103(4):470-4. doi: 10.1007/s004390050852.
Wolfram syndrome (MIM 222300) is characterized by juvenile-onset diabetes mellitus and optic atrophy. Previous linkage analyses in the United States and UK families have indicated that the gene for Wolfram syndrome (WFS) is localized on the short arm of chromosome 4. We herein confirm the linkage of the WFS locus to D4S3023 on 4p with a two-point LOD score of 3.42 in a large Japanese family with Wolfram syndrome. Multipoint linkage analysis revealed the maximum LOD score of 4.82 between D4S3023 and D4S394. We also evaluated putative health risks in carriers by multiple logistic analysis with independent variables, age, gender, and numbers of affected haplotypes and with dependent variables, such as hearing loss, diabetes mellitus, polyuria, incontinence, psychological illness, and visual acuity. The results showed that the putative disease haplotype increased a risk of hearing loss (odds ratio =35.68, 95% confidence interval =4.12-308.95) and diabetes mellitus (odds ratio =7.57, 95% confidence interval =2.03-28.23) independently. This is the first report of an increased health risk of illness in carriers, other than for psychiatric disease.
沃夫勒姆综合征（MIM 222300）的特征为青少年期发病的糖尿病和视神经萎缩。此前在美国和英国家庭中进行的连锁分析表明，沃夫勒姆综合征（WFS）基因定位于4号染色体短臂。我们在此证实，在一个患沃夫勒姆综合征的大型日本家族中，WFS基因座与4p上的D4S3023连锁，两点连锁分析的LOD值为3.42。多点连锁分析显示，D4S3023与D4S394之间的最大LOD值为4.82。我们还通过多因素逻辑分析评估了携带者的潜在健康风险，自变量为年龄、性别和受累单倍型数量，因变量为听力损失、糖尿病、多尿、尿失禁、心理疾病和视力。结果显示，假定的疾病单倍型分别独立增加了听力损失（优势比=35.68，95%置信区间=4.12 - 308.95）和糖尿病（优势比=7.57，95%置信区间=2.03 - 28.23）的风险。这是关于携带者（除精神疾病外）患病健康风险增加的首次报道。
