Microarray-Based Mutation Analysis of 183 Spanish Families with Usher Syndrome
Microarray-Based Mutation Analysis of 183 Spanish Families with Usher Syndrome
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DOI：
10.1167/iovs.09-4085
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发表时间：
2010-03-01
影响因子：
4.4
通讯作者：
Millan, Jose M.
中科院分区：
文献类型：
--
作者：
Jaijo, Teresa;Aller, Elena;Millan, Jose M.
目的.本研究的目的是检测Usher综合征（USH）基因分型芯片在183例USH患者队列中识别致病突变的能力。来自西班牙人群的183例Usher综合征患者的DNA使用基因分型微阵列进行分析，该基因分型微阵列包含8个USH基因中429个先前确定的疾病相关变异。通过直接测序确认通过阵列检测的突变。在携带常见西班牙突变的家庭中也进行了单倍型分析。基因分型微阵列鉴定了43种不同的变体，分为32种致病性变体和11种可能非病理性变体。在62例USH患者中检测到突变（33.9%）。按临床分型，USH 1型31.4%，USH 2型39.4%，USH 3型22.2%，未分型Usher综合征15.8%。检测到97个病理等位基因，占预期等位基因的26.5%。USH 2A突变p.C3267R和p.T3571M在西班牙人群中很常见，与这些突变相关的两种主要单倍型被排除。基因分型微阵列是一种稳健、低成本、快速的技术，可有效用于USH患者的遗传研究。然而，它也表明，还观察到了病理性质不清楚的变体和检测失败。结果必须通过直接测序来确认，以避免误诊，并应进行芯片的不断更新，以提高突变的检测效率和速度。（Invest Ophthalmol维斯科学。2010;51：1311-1317）DOI：10.1167/iovs.09-4085
PURPOSE. The purpose of this study was to test the ability of the genotyping microarray for Usher syndrome (USH) to identify the mutations responsible for the disease in a cohort of 183 patients with USH.METHODS. DNA from 183 patients with Usher syndrome from the Spanish population was analyzed using a genotyping microarray containing 429 previously identified disease-associated variants in eight USH genes. Mutations detected by the array were confirmed by direct sequencing. Haplotype analysis was also performed in families carrying common Spanish mutations.RESULTS. The genotyping microarray identified 43 different variants, divided into 32 disease causative and 11 probably non-pathologic. Mutations were detected in 62 patients with USH (33.9%). According to the clinical classification of patients, pathologic variants were detected in 31.4% patients with USH1, 39.4% of with USH2, 22.2% with USH3 and 15.8% with unclassified Usher syndrome. Ninety-seven pathologic alleles were detected, corresponding to 26.5% of expected alleles. The USH2A mutations p. C3267R and p. T3571M were revealed as common in the Spanish population, and two major haplotypes linked to these mutations were observed.CONCLUSIONS. The genotyping microarray is a robust, low-cost, rapid technique that is effective for the genetic study of patients with USH. However, it also indicates variants of unclear pathologic nature and detection failures have also been observed. Results must be confirmed by direct sequencing to avoid misdiagnosis, and continuous updates of the microarray should be performed to increase the efficiency and rate of detection of mutations. (Invest Ophthalmol Vis Sci. 2010;51:1311-1317) DOI:10.1167/iovs.09-4085