Tug E, Percin F E, Pala E, Baysoy G
Department of Medical Genetics, Abant Izzet Baysal University Izzet Baysal Medical School, Bolu-Turkey.
Genet Couns. 2011;22(2):143-53.
Alport syndrome (AS) is a renal disease that is characterized by proteinuria and progressive renal failure, and often accompanied by sensorineural hearing loss and ocular changes. Mutations in the genes encoding for three members of the type IV collagen protein family have been found to be the cause of the disease. We describe a large Turkish family with X-linked AS. We performed linkage analysis in this family and sequencing to identify the mutation in the proband whose disease was confirmed by renal biopsy.
After genomic DNAs extracted, linkage to the COL4A5 locus was examined using the 2B6 and 2B20, DXS1106, DXS1105 and COL4A5 markers. In addition, COL4A5 gene sequence analysis was performed in the proband.
Genetic linkage analysis demonstrated co-segregation of the disease. Haplotype analysis showed that the same haplotype was carried by all affected males and obligatory carrier females. Mutation analysis of the proband has revealed a novel nonsense mutation (c.1135C>T; Gln379X) in exon 19 of the COL4A5 gene which may lead to a more severe phenotype in affected family members carrying this mutation. According to GenBank data base, this mutation has not been reported previously.
Genetic testing identified a previously undescribed COL4A5 mutation as the cause of the disease.
奥尔波特综合征（AS）是一种以蛋白尿和进行性肾衰竭为特征的肾脏疾病，常伴有感音神经性听力损失和眼部病变。已发现编码IV型胶原蛋白家族三个成员的基因突变是该疾病的病因。我们描述了一个患有X连锁AS的大型土耳其家族。我们在这个家族中进行了连锁分析和测序，以确定先证者的突变，其疾病经肾活检确诊。
提取基因组DNA后，使用2B6和2B20、DXS1106、DXS1105和COL4A5标记检查与COL4A5基因座的连锁情况。此外，对先证者进行了COL4A5基因序列分析。
遗传连锁分析表明疾病共分离。单倍型分析显示，所有受影响的男性和 obligatory carrier女性都携带相同的单倍型。先证者的突变分析揭示了COL4A5基因第19外显子中的一个新的无义突变（c.1135C>T；Gln379X），这可能导致携带该突变的受影响家庭成员出现更严重的表型。根据GenBank数据库，该突变此前尚未见报道。
基因检测确定了一种先前未描述的COL4A5突变是该疾病的病因。
