Phenotype-genotype correlations in a series of Wolfram syndrome families

被引:79
作者
Smith, CJA
Crock, PA
King, BR
Meldrum, CJ
Scott, RJ [3 ]
机构
[1] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2308, Australia
[2] Univ Newcastle, Fac Hlth, Discipline Med Genet, Newcastle, NSW 2308, Australia
[3] John Hunter Hosp, Hunter Area Pathol Serv, Div Genet, Newcastle, NSW 2310, Australia
[4] Univ Newcastle, John Hunter Childrens Hosp, Newcastle, NSW 2308, Australia
关键词
D O I
10.2337/diacare.27.8.2003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE - Wolfram syndrome is an extremely rare autosomal-recessive disorder that predisposes the development of type 1 diabetes in association With progressive optic atrophy. The genetic basis of this disease has been shown to be due to mutations in the WFS1 gene. The WFS1 gene encodes a novel transmembrane protein called wolframin, which recent evidence suggests may serve as a novel endoplasmic reticulum calcium channel in pancreatic beta-cells and neurons. Genotype-phenotype correlations in this syndrome are becoming apparent and may help in explaining some of the variable characteristics observed in this disease. RESEARCH DESIGN AND METHODS - in this report, we have Studied 13 patients -,with Wolfram syndrome from nine families to further define the relationship between mutation Site and type With specific disease characteristics. RESULTS - A severe phenotype was seen in patients with mutations in exon 4 and with a large deletion encompassing most of exert 8. In total, nine novel mutations were identified as well as three new silent polymorphisms. CONCLUSIONS - Similar to all Other Mutation reports, most causative changes identified in the WFS1 gene occurred in exon 8, and only one was identified Outside this region in exon 4.
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收藏
页码:2003 / 2009
页数:7
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