ALPORT SYNDROME GENETICS AND MUTATION DETECTION

描述：COL4A5基因缺陷，该基因编码不同的 基底膜胶原α 5（V），最近已被证明在 Alport综合征（AS），一种遗传性进行性肾小球肾炎。 的 疾病表现出大量的表型变异，类似于骨生成 Colta，其中COL1A1和COL1A2中的各种缺陷导致骨 具有非常广泛的表型严重性的脆弱性。 在AS中， 疾病随相关耳聋的严重程度而变化， 发病和终末期肾病（需要肾移植）的年龄 或永久性透析治疗），以及特征性眼和 血液异常 听力损失的变异性似乎是由于 COL4A5的等位基因变异，因为两个突变完全位于 这种基因导致不同程度的耳聋。 申请人建议 进行基因研究，以确定是否有任何遗传缺陷， Alport家族位于COL4A5以外的位点。 作为合作的一部分， 努力，申请人将检查COL4A5基因的突变， 缺陷似乎存在于该位点的家庭。 全面 将由合作者对这些家族进行临床表征， 这些研究将共同构成相关性的基础 具有不同表型的分子缺陷。 建立这个 相关性将提高治疗干预的疗效， 疾病，并导致更好地了解COL4A5在疾病中的作用。 基底膜的分子结构，也许暗示了一些 干预疾病进展过程的手段。 的 新的COL4A5突变的起源情况也将被检查 以确定是否有任何重要的风险因素。

DESCRIPTION: Defects in the COL4A5 gene, which encodes the distinct basement membrane collagen alpha5(V), have recently been demonstrated in Alport Syndrome (AS), a hereditary progressive glomerulonephritis. The disease shows substantial phenotypic variation, similar to osteogenesis imperfecta, where various defects in COL1A1 and COL1A2 cause bone fragility with a very wide range of phenotypic severity. In AS, the disease varies with respect to the severity of associated deafness, the age of onset and end-stage renal disease (which requires kidney transplant or permanent dialysis therapy), and the presence of characteristic eye and blood abnormalities. The variability of hearing loss appears to be due to allelic variation at COL4A5, since two mutations which lie entirely within the gene cause deafness of different severities. The applicants propose to perform genetic studies to determine if the genetic defect in any Alport family is at a locus other than COL4A5. As part of a collaborative effort, the applicants will examine the COL4A5 gene for mutation in families where the defect appears to reside at this locus. Comprehensive clinical characterization of these families by collaborators will be conducted and together these studies will form the basis for a correlation of the molecular defects with the variable phenotypes. Establishing this correlation will improve the efficacy of therapeutic intervention in the disease and lead to a better understanding of the role of COL4A5 in the molecular architecture of the basement membrane, perhaps suggesting some means of intervening in the progressive disease process. The circumstances of the origin of new COL4A5 mutations will also be examined to determine if there are any important risk factors.