Genotype-Phenotype Correlations in 17 Chinese Patients With Autosomal Recessive Alport Syndrome
Genotype-Phenotype Correlations in 17 Chinese Patients With Autosomal Recessive Alport Syndrome
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DOI：
10.1002/ajmg.a.35528
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发表时间：
2012-09-01
影响因子：
2
通讯作者：
Wang, Suxia
中科院分区：
文献类型：
--
作者：
Zhang, Yanqin;Wang, Fang;Wang, Suxia
常染色体隐性遗传 Alport 综合征 (ARAS) 由 COL4A3 或 COL4A4 基因突变引起。我们分析了 17 名无关的中国 ARAS 患者的基因型和表型。审查了临床数据。 COL4A3 和 COL4A4 基因的所有编码外显子均通过基因组 DNA 进行 PCR 扩增和测序。我们对所有患者进行了病理突变检测，突变检出率为100%，其中COL4A3基因突变检出率为82%，COL4A4基因突变检出率为18%。鉴定出 COL4A3 基因中的 16 个新突变和 COL4A4 基因中的 4 个新突变。此外，在我们的研究中，在四名患者中发现了先前报道的 COL4A3 基因外显子 1 的框内缺失突变 (40_63del24)。 COL4A3 中的单个 40_63del24 突变似乎会导致轻微或无肾脏症状，而 COL4A3 基因中的 40_63del24 纯合状态或 40_63del24 的复合杂合突变加上 COL4A3 基因中的另一个无义或移码突变似乎会导致严重的 ARAS 并伴有听力损失。一半的先证者父母有血尿，伴或不伴轻度蛋白尿。因此，我们建议当患者有血尿阳性家族史时考虑ARAS，首先筛查COL4A3突变可能是ARAS分子诊断的有效策略。 (C) 2012 年 Wiley 期刊公司。
Autosomal recessive Alport syndrome (ARAS) results from mutations in the COL4A3 or COL4A4 gene. We analyzed the genotype and phenotype of 17 unrelated Chinese patients with ARAS. Clinical data were reviewed. All coding exons of COL4A3 and COL4A4 genes were PCR-amplified and sequenced from genomic DNA. We identified pathologic mutations in all patients, giving a mutation detection rate of 100%, with 82% in COL4A3 gene and 18% in COL4A4 gene. Sixteen novel mutations in COL4A3 gene and four novel mutations in COL4A4 gene were identified. Furthermore, a previously reported in-frame deletion mutation (40_63del24) in exon 1 of the COL4A3 gene was found in four patients in our study. A single 40_63del24 mutation in COL4A3 seems to result in mild or no renal manifestations, whereas the homozygous state of 40_63del24 in COL4A3 gene or compound heterozygous mutation of 40_63del24 plus another nonsense or frameshift mutation in COL4A3 gene seems to result severe ARAS with hearing loss. Half of the probands' parents had hematuria with or without mild proteinuria. Therefore, we recommend that ARAS be considered when a patient has a positive family history of hematuria, and screening for COL4A3 mutations firstly may be an efficient strategy for molecular diagnosis of ARAS. (C) 2012 Wiley Periodicals, Inc.