Mirrahimi Mehraban, Safi Sare, Mohammadzadeh Maryam, Doozandeh Azadeh, Suri Fatemeh
Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Ophthalmic Epidemiology Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Ophthalmic Vis Res. 2021 Oct 25;16(4):602-610. doi: 10.18502/jovr.v16i4.9750. eCollection 2021 Oct-Dec.
To study the genetic basis and clinical manifestations of Wolfram syndrome in a multi-affected family.
Complete clinical examinations including urological, ophthalmic, neurological, and endocrinologic assessment were performed for three affected family members. Genomic DNA was extracted from peripheral blood leukocytes with salting out method and all exons and their flanking regions were sequenced. Candidate variation was screened for segregation in the pedigree by Sanger sequencing.
A known pathogenic missense mutation in gene (c.1885C T which leads to p.Arg629Trp in the encoded protein) was identified in all affected individuals. Both clinical and genetic investigations confirmed Wolfram syndrome diagnosis with variable phenotypic features.
Identical mutations in the Wolfram syndrome causative gene can lead to variable manifestations of the syndrome even in the same family. Although the medical findings and clinical examination are imperative for the diagnosis of Wolfram syndrome, genetic testing is useful to confirm the diagnosis, especially in cases with possible reduced penetrance of the characteristic signs.
研究一个多成员患病家庭中沃尔弗拉姆综合征的遗传基础和临床表现。
对三名患病家庭成员进行了包括泌尿外科、眼科、神经科和内分泌科评估在内的全面临床检查。采用盐析法从外周血白细胞中提取基因组DNA，并对所有外显子及其侧翼区域进行测序。通过桑格测序法筛选候选变异在系谱中的分离情况。
在所有患病个体中均鉴定出一个已知的致病基因错义突变（c.1885C>T，导致编码蛋白中的p.Arg629Trp）。临床和基因研究均证实了具有可变表型特征的沃尔弗拉姆综合征诊断。
即使在同一家族中，沃尔弗拉姆综合征致病基因的相同突变也可导致该综合征的可变表现。虽然医学检查结果和临床检查对于沃尔弗拉姆综合征的诊断至关重要，但基因检测有助于确诊，尤其是在特征性体征可能外显率降低的病例中。
