Molecular testing for adult type Alport syndrome.
Molecular testing for adult type Alport syndrome.
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DOI：
10.1186/1471-2369-10-38
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发表时间：
2009-11-17
期刊：
影响因子：
2.3
通讯作者：
Lyon E
中科院分区：
文献类型：
--
作者：
Pont-Kingdon G;Sumner K;Gedge F;Miller C;Denison J;Gregory M;Lyon E
Alport综合征（AS）是一种累及耳蜗和眼部的进行性肾病。大多数AS病例是X连锁的（XLAS），并且是由于COL4A5基因突变引起的。虽然这种疾病可能出现在生命的早期，并在年轻人中进展为终末期肾病（ESRD），但在其他家族中，ESRD发生在中年。在COL4A5中描述的400多个突变中，很少有与成人型XLAS相关，但这些家族可能非常大。我们根据美国的患病率对成人AS型突变进行了分类，并使用一组杂交探针开发了一种分子检测方法，可识别三种最常见的成人XLAS型突变：C1564S、L1649R和R1677Q。在先前确定含有这些突变中的一种或不含有这些突变的样品上验证了该测试。在美国，该测试的临床特异性和敏感性估计分别高于99%和75%。分析特异性和灵敏度均在99%以上。这种测试可能是有用的症状前和携带者测试在家庭中的突变之一，并在不明原因的血尿或慢性肾脏疾病的诊断。
Alport syndrome (AS) is a progressive renal disease with cochlear and ocular involvement. The majority of AS cases are X-linked (XLAS) and due to mutations in the COL4A5 gene. Although the disease may appear early in life and progress to end stage renal disease (ESRD) in young adults, in other families ESRD occurs in middle age. Few of the more than four hundred mutations described in COL4A5 are associated with adult type XLAS, but the families may be very large. We classified adult type AS mutation by prevalence in the US and we developed a molecular assay using a set of hybridization probes that identify the three most common adult type XLAS mutations; C1564S, L1649R, and R1677Q. The test was validated on samples previously determined to contain one or none of these mutations. In the US, the test's clinical specificity and sensitivity are estimated to be higher than 99% and 75% respectively. Analytical specificity and sensitivity are above 99%. This test may be useful for presymptomatic and carrier testing in families with one of the mutations and in the diagnosis of unexplained hematuria or chronic kidney disease.