分子病検査診断「症例呈示と病態解析」(4)

糖尿病の遺伝子診断 : Wolfram 症候群
−ポジショナルクローニングから遺伝子診断へ−

谷　澤　幸　生*
　　　　　　　　　　　　　　　　　　　　　　
Genetic Diagnosis of Diabetes Mellitus : Wolfram Syndrome
−From Positional Cloning to DNA Diagnosis−

Yukio TANIZAWA, MD, PhD*

Wolfram syndrome(WFS, DIDMOAD syndrome) is an autosomal recessive neurodegenerative disorder characterized by juvenile-onset, insulin-dependent diabetes mellitus and optic atrophy, often accompanied by other symptoms including diabetes insipidus, neurosensory deafness, urinary tract and neurological abnormalities. In patients, b -cells are selectively lost from their pancreatic islets of Langerhans. By positional cloning, a novel gene named WFS1 was identified and many mutations were subsequently identified in patients with WFS. Most of the mutations were identified in the largest 8th exon, however, they also existed in other exons. No common mutations were found and founder effect was not observed except in Spanish families. The WFS1 gene encodes a putative transmembrane protein of 100.3 kDa localized in endoplasmic reticulum. More recently, WFS1 mutations were also identified in patients with dominantly inherited low-frequency sensorineural hearing loss. Clarification of the functions of the WFS1 protein, as well as the phenotype-genotype relationship, will help improve understanding of the pathophysiology of diseases caused by the WFS1 gene.
[Rinsho Byori 51 : 544〜549, 2003]

*Division of Molecular Analysis of Human Disorders, Department of Bio-Signal Analysis, Yamaguchi University Graduate School of Medicine, Ube 755-8505

【Key Words】Wolfram syndrome(Wolfram 症候群)，diabetes mellitus(糖尿病)，optic atrophy(視神経萎縮)，positional cloning(ポジショナルクローニング)

*山口大学大学院医学研究科生体シグナル解析医学講座分子病態解析学(〒755-8505 宇部市南小串1-1-1)

E-mail :tanizawa@yamaguchi-u.ac.jp