Department of Pediatrics, Peking University First Hospital, Beijing, China.
J Mol Diagn. 2012 Nov;14(6):586-93. doi: 10.1016/j.jmoldx.2012.06.005. Epub 2012 Aug 21.
A total of 209 unrelated patients of predominantly Han Chinese ethnicity and with X-linked Alport's syndrome, a clinically heterogeneous hereditary nephritis, were enrolled in the present study to evaluate the ability to make a clinical diagnosis and perform molecular genetics analysis using skin biopsy. A negative or mosaic α5(IV) chain staining in the epidermal basement membrane was detected in 86.2% of male and 93.5% of female patients. COL4A5 mutations were identified in 85% of male patients with a negative α5(IV) chain staining pattern in the epidermal basement membrane. With use of skin biopsy and immunostaining, 16.4% of our patients were diagnosed before 3 years of age, and the youngest was diagnosed at 1 year of age. COL4A5 mutations were detected in 22 patients with normal epidermal basement membrane staining for the α5(IV) chain. Analysis of COL4A5 cDNA fragments from skin fibroblasts yielded a mutation detection rate of 83%, which was particularly valuable for identification of cryptic splicing mutations. Furthermore, 83% of COL4A5 mutations identified in the present study were novel. Thus, skin biopsy is a practical approach for the clinical diagnosis and molecular genetic analysis of X-linked Alport's syndrome.
本研究共纳入 209 例汉族散发性 X 连锁 Alport 综合征患者，该疾病是一种临床表现异质性的遗传性肾炎，旨在评估皮肤活检在临床诊断和分子遗传学分析中的应用价值。86.2%的男性和 93.5%的女性患者的表皮基底膜 α5(IV)链染色呈阴性或镶嵌状。在表皮基底膜 α5(IV)链染色阴性的男性患者中，85%存在 COL4A5 突变。利用皮肤活检和免疫组化，我们有 16.4%的患者在 3 岁之前得到诊断，最小的诊断年龄为 1 岁。22 例表皮基底膜 α5(IV)链染色正常的患者检测到 COL4A5 突变。从皮肤成纤维细胞的 COL4A5 cDNA 片段分析中，突变检测率为 83%，这对于鉴定隐匿性剪接突变特别有价值。此外，本研究中鉴定的 83%的 COL4A5 突变是新的。因此，皮肤活检是 X 连锁 Alport 综合征临床诊断和分子遗传学分析的实用方法。
