A family-analysis-based search for genes susceptible to mono-, oligo- and polygenic disorders

我们试图通过基因组医学方法分离或鉴定疾病相关基因，使用的是有单基因、少基因或多基因疾病的家系。在为期五年的研究中，我们确定了决定人类耳垢类型的基因，即导致先天性白内障的基因，以及家族性日本热、手脚分裂和先天性缺钉的候选基因。我们定位了原发性手掌多汗症、家族性上睑下垂、软腭裂、家族性动静脉畸形、发作性运动性舞蹈手足徐动症和Dupuytren挛缩症的基因座。我们还通过候选基因分析在一个家族性房间隔缺陷症家系中发现了一个新的突变。然而，尽管对歌舞伎综合征、先天性鼻音障碍和2型糖尿病患者的染色体易位断裂点进行了分析，但仍发现了任何致病基因。

We tried to isolate or identify disease-related genes by genomic-medicine methods using families with monogenic, oligogenic or polygenic disorders. During a five-year period of study, we identified the gene determining human earwax type, gene responsible for a congenital cataract, and those candidate for familial Japan fever, split hands and feet, and congenital absence of nails. We mapped gene loci for primary palmar hyperhidrosis, familial blepharoptosis, cleft soft palate, familial arteriovenous malformation, paroxysmal kinesigenic choreoathetosis, and Dupuytren contracture. We also identified a novel mutation in a family with familial atrial septal defect by a candidate gene analysis. However, although chromosomal translocation breakpoints were analyzed in patients with Kabuki syndrome, congenital arhinia and type 2 diabetes mellitus, any causative genes were found.