Cano A, Rouzier C, Monnot S, Chabrol B, Conrath J, Lecomte P, Delobel B, Boileau P, Valero R, Procaccio V, Paquis-Flucklinger V, Vialettes B
Department of Nutrition, Metabolic Diseases and Endocrinology, la Timone, Hospital, Marseille, France.
Am J Med Genet A. 2007 Jul 15;143A(14):1605-12. doi: 10.1002/ajmg.a.31809.
Mutations in the WFS1 gene have been reported in Wolfram syndrome (WS), an autosomal recessive disorder defined by early onset of diabetes mellitus (DM) and progressive optic atrophy. Because of the low prevalence of this syndrome and the recent identification of the WFS1 gene, few data are available concerning the relationships between clinical and molecular aspects of the disease. Here, we describe 12 patients from 11 families with WS. We report on eight novel (A214fsX285, L293fsX303, P346L, I427S, V503fsX517, R558C, S605fsX711, P838L) and seven previously reported mutations. We also looked for genotype-phenotype correlation both in patients included in this study and 19 additional WS patients that were previously reported. Subsequently, we performed a systematic review and meta-analysis of five published clinical and molecular studies of WFS1 for genotype-phenotype correlation, combined with our current French patient group for a total of 96 patients. The presence of two inactivating mutations was shown to predispose to an earlier age of onset of both DM and optic atrophy. Moreover, the clinical expression of WS was more complete and occurred earlier in patients harboring no missense mutation.
WFS1基因的突变已在沃夫勒姆综合征（WS）中被报道，这是一种常染色体隐性疾病，其特征为糖尿病（DM）的早发和进行性视神经萎缩。由于该综合征的患病率较低，且WFS1基因是最近才被鉴定出来的，因此关于该疾病临床和分子方面之间关系的数据很少。在此，我们描述了来自11个家庭的12例WS患者。我们报告了8个新的突变（A214fsX285、L293fsX303、P346L、I427S、V503fsX517、R558C、S605fsX711、P838L）和7个先前报道过的突变。我们还在本研究纳入的患者以及另外19例先前报道的WS患者中寻找基因型与表型的相关性。随后，我们对已发表的5项关于WFS1基因与基因型-表型相关性的临床和分子研究进行了系统综述和荟萃分析，并将其与我们目前的法国患者组相结合，总共涉及96例患者。结果显示，存在两个失活突变会使糖尿病和视神经萎缩的发病年龄更早。此外，在没有错义突变的患者中，WS的临床表型更完整且出现得更早。
