Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark.
BMC Med Genet. 2011 Apr 4;12:49. doi: 10.1186/1471-2350-12-49.
Autosomal dominant optic atrophy (ADOA, Kjer disease, MIM #165500) is the most common form of hereditary optic neuropathy. Mutations in OPA1 located at chromosome 3q28 are the predominant cause for ADOA explaining between 32 and 89% of cases. Although deletions of OPA1 were recently reported in ADOA, the frequency of OPA1 genomic rearrangements in Denmark, where ADOA has a high prevalence, is unknown. The aim of the study was to identify copy number variations in OPA1 in Danish ADOA patients.
Forty unrelated ADOA patients, selected from a group of 100 ADOA patients as being negative for OPA1 point mutations, were tested for genomic rearrangements in OPA1 by multiplex ligation probe amplification (MLPA). When only one probe was abnormal results were confirmed by additional manually added probes. Segregation analysis was performed in families with detected mutations when possible.
Ten families had OPA1 deletions, including two with deletions of the entire coding region and eight with intragenic deletions. Segregation analysis was possible in five families, and showed that the deletions segregated with the disease.
Deletions in the OPA1 gene were found in 10 patients presenting with phenotypic autosomal dominant optic neuropathy. Genetic testing for deletions in OPA1 should be offered for patients with clinically diagnosed ADOA and no OPA1 mutations detected by DNA sequencing analysis.
常染色体显性视神经萎缩（ADOA，Kjer 病，MIM#165500）是最常见的遗传性视神经病变形式。位于 3q28 染色体上的 OPA1 突变是 ADOA 的主要原因，占 32%至 89%的病例。尽管最近在 ADOA 中报道了 OPA1 的缺失，但丹麦 ADOA 发病率较高，OPA1 基因组重排的频率尚不清楚。本研究旨在鉴定丹麦 ADOA 患者 OPA1 中的拷贝数变异。
从 100 名 ADOA 患者中选择的 40 名不携带 OPA1 点突变的无关 ADOA 患者，通过多重连接探针扩增（MLPA）检测 OPA1 中的基因组重排。当只有一个探针异常时，通过额外手动添加的探针确认结果。当可能时，对具有检测到突变的家系进行分离分析。
10 个家系存在 OPA1 缺失，包括 2 个整个编码区缺失和 8 个内含子缺失。在 5 个家系中可以进行分离分析，结果显示缺失与疾病共分离。
在表现为常染色体显性视神经病变的 10 名患者中发现了 OPA1 基因缺失。对于临床诊断为 ADOA 且未通过 DNA 测序分析检测到 OPA1 突变的患者，应提供 OPA1 缺失的基因检测。
