Heterozygous deletion of the OPA1 gene in patients with dominant optic atrophy.
Heterozygous deletion of the OPA1 gene in patients with dominant optic atrophy.
复制标题
显性视神经萎缩患者 OPA1 基因杂合缺失。
DOI：
10.1007/s10384-017-0522-0
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Tsuneoka H.
中科院分区：
文献类型：
--
作者：
Hayashi T;Sasano H;Katagiri S;Tsunoda K;Kameya S;Nakazawa M;Iwata T;Tsuneoka H.
目的几种OPA1基因变异导致遗传性视神经萎缩(DOA)，这是最常见的遗传性视神经萎缩。在这里，我们描述了在3名DOA患者中新发现的OPA1缺失。方法女性先证者、她的兄弟和她的母亲接受了完整的眼科检查，包括使用Humphrey视野分析仪进行光学相干断层扫描和视野评估，同时使用标准自动视野检查(SAP)和短波自动视野检查(SWAP)。检测每个患者的基因组DNA以检测涉及OPA1的基因组重排；基因分析包括多重连接探针扩增和常规Sanger测序。结果每个患者都有颞叶视盘苍白和双眼视网膜神经纤维层明显变薄，尽管患者之间存在表型差异，从无症状到中度视力下降。对于受影响的兄弟和母亲，SAP的平均偏差值在正常范围内，而SWAP的平均偏差值显著低于正常范围(P<；10.05)。遗传分析发现了一个新发现的包含外显子9-14的杂合性缺失，并发现了一个直接连接内含子8和内含子14的断点连接。结论这一新发现的缺失可能导致由外显子9-16编码的具有重要功能的GTP酶结构域的功能丧失，这种杂合性表明单倍体不足导致了表型。缺失可能与轻度DOA表型有关，范围从无症状到中度视力下降。
PurposeSeveralOPA1variants cause dominant optic atrophy (DOA), the most common hereditary optic atrophy. Here, we describe a newly discoveredOPA1deletion in 3 patients with DOA.MethodsA female proband, her brother, and her mother underwent complete ophthalmologic examinations that included optical coherence tomography and visual field assessments using a Humphrey Field Analyzer with both standard automated perimetry (SAP) and short-wavelength automated perimetry (SWAP). Genomic DNA from each patient was examined to detect genomic rearrangements involvingOPA1; the genetic analysis involved both multiplex ligation probe amplification and conventional Sanger sequencing.ResultsEach patient had temporal optic disc pallor and significant thinning of the retinal nerve fiber layer in both eyes, although there was phenotypic variability among the patients that ranged from asymptomatic to moderately decreased visual acuity. For the affected brother and mother, the mean deviation values from SAP were within the normal range, whereas those from SWAP were significantly below the normal range (P< .05). The genetic analysis identified a newly discovered heterozygous deletion that encompasses exons 9–14 and revealed a breakpoint junction that directly connects intron 8 to intron 14.ConclusionsThis newly described deletion is likely to lead to loss of function in the functionally important GTPase domain encoded by exons 9–16, and the heterozygosity suggested that haploinsufficiency caused the phenotypes. The deletion may be associated with mild DOA phenotypes ranging from asymptomatic to moderately decreased visual acuity.