The OPA1 gene mutations in patients with autosomal dominant optic atrophy and associated morphological and physiological changes.

常染色体显性视神经萎缩患者的 OPA1 基因突变及相关形态和生理变化。

• 批准号: 16591746
• 负责人: NAKAMURA Makoto
• 金额: $ 2.18万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591746/
• 关键词: autosomal dominant optic atrophy; molecular genetics; OPA1; sporadic case; optical coherence tomography; retinal nerve fiber layer; cone electroretinogram; photopic negative response; 遺伝子変異; ホットスポット; OCT3

The OPA1 gene was examined in Japanese patients with autosomal dominant optic atrophy (ADOA), and 11 different heterozygous mutations in the gene were detected in 13 unrelated families. We detected an OPA1 mutation in 8/9 familial cases with optic atrophy indicating that the OPA1 gene mutations are causative in most familial cases with ADOA in Japanese. We detected a mutation in 5/10 cases that were initially considered to be sporadic from their family histories, indicating that sporadic cases with optic atrophy may also be frequently caused by OPA1 mutations in Japanese population. The identified mutations included five deletions/insertions, four nonsense, one splice site, and one missense mutations. Because most of the mutations were truncative mutations or splice site mutations, the mechanism of haplo-insufficiency was suggested to be involved in the pathogenesis of ADOA. The most common mutation in Caucasians (c.2708_2711delTTAG) was found in three unrelated families, suggesting th … More at it is a mutational hot spot.The morphological changes in the macular area were determined in patients with the OPA1 mutations. The thickness of the retinal nerve fiber layer (RNFL) in the macular area was significantly thinner in the ADOA patients than that in controls. The thickness of the layer including the ganglion cell layer was also significantly thinner in the patients. The thickness of the outer retina was not significantly different between the ADOA patients and normal controls, thus we confirmed that the inner retina is the main area of the retina altered morphologically by this disease.The amplitudes of photopic negative response (PhNR) in full-field electroretinogram (ERG), which are considered to reflect the function of inner retina, were significantly smaller in the patients ADOA than those in controls. Although it is generally believed that patients with ADOA have normal b-wave amplitudes in full-field ERG, we found a case of optic atrophy associated with an OPA1 mutation whose b-wave was reduced showing negative ERG waveform. We could find no correlation between clinical severity and genotype. Less

在日本常染色体显性视神经萎缩（ADOA）患者中检测OPA 1基因，在13个无关家族中检测到11种不同的杂合突变。我们在8/9例家族性视神经萎缩病例中检测到OPA 1突变，表明OPA 1基因突变是日本大多数ADOA家族性病例的病因。我们在最初被认为是家族史散发的5/10例病例中检测到突变，表明日本人群中的OPA 1突变也可能经常引起视神经萎缩的散发病例。鉴定的突变包括5个缺失/插入、4个无义突变、1个剪接位点和1个错义突变。由于突变多为截短突变或剪接位点突变，提示单倍体功能不全机制参与了ADOA的发病。高加索人中最常见的突变（c.2708_2711delTTAG）在三个无关的家族中发现，这表明 ...更多信息 OPA 1基因突变患者黄斑区的形态学改变。黄斑区视网膜神经纤维层（RNFL）厚度在ADOA组明显小于对照组。包括神经节细胞层在内的层的厚度在患者中也显著变薄。ADOA患者视网膜外层厚度与正常对照组无明显差异，证实了视网膜内层是ADOA视网膜形态改变的主要区域，而反映视网膜内层功能的全视野视网膜电图（full-field electroretinogram，ERG）明视负反应（photopic negative response，PhNR）振幅在ADOA患者明显低于正常对照组。虽然一般认为ADOA患者在全视野ERG中具有正常的b波振幅，但我们发现一例与OPA 1突变相关的视神经萎缩，其b波降低，显示负性ERG波形。我们没有发现临床严重程度与基因型之间的相关性。少

项目成果

Case of chromosome 6p25 terminal deletion associated with Axenfield-Rieger syndrome and persistent hyperplastic primary vetreous.

与 Axenfield-Rieger 综合征和持续性原发性椎体增生相关的染色体 6p25 末端缺失病例。

• 发表时间: 2006
• 期刊: Am J Med Genet A 140
• 作者: 黒田 知子;片井 直達;等;Ishikawa K.et al.;Suzuki K
• 通讯作者: Suzuki K

Case of chromosome 6p25 terminal deletion associated with Axenfeld-Rieger syndrome and persistant hyperplastic primary vitreous.

与 Axenfeld-Rieger 综合征和持续性原发性玻璃体增生相关的染色体 6p25 末端缺失病例。

• 发表时间: 2006
• 期刊: Am J Med Genet A. 140
• 作者: Suzuki;K.
• 通讯作者: K.

Novel mutations in OPA 1 gene and associated clinical features in Japanese patients with optic atrophy.

日本视神经萎缩患者 OPA 1 基因的新突变及相关临床特征。

• 发表时间: 2006
• 期刊: Ophthalmology (in press)
• 作者: Matsubara A;et al.;Matsubara A;Suzuki K.( et al.;Nakamura M.( et al.
• 通讯作者: Nakamura M.( et al.

Acquired unilateral night blindness with negative ERG : nine-year follow-up.

ERG 阴性的获得性单侧夜盲症：九年随访。

• 发表时间: 2005
• 期刊: Retina 25(4)
• 作者: Matsubara A;et al.;Matsubara A;Suzuki K.( et al.;Nakamura M.( et al.;Nakamura M.( et al.;Kondo M.( et al.;Ueno S.( et al.;Hotta K.( et al.;Yoshida T.( et al.;Machida S.( et al.;Matsunuma H.( et al.;Mase J.( et al.;Ohno K.( et al.;Suzuki K;Nakamura M;Nakamura M;Kondo M;Ueno S;Hotta K;Yoshida T;Machida S;Matsunuma H;Mase J;Ohno K;Suzuki K.(et al.);Nakamura M. (et al.);Nakamura M. (et al.);Kondo M.(et al.);Ueno S.(et al.);Hotta K.(et al.);Yoshida T. (et al.);Machida S. (et al.);Matsunuma H. (et al.);Mase J.(et al.);Ohno K.(et al.);Niwa Y.( et al.;Ito Y.( et al.;Ito A.( et al.;Uemura A.( et al.;Komeima K.( et al.;Niwa H.( et al.;Kobayashi C.( et al.;Kito K.( et al.;Yamada M.( et al.;Ishikawa K.( et al.;Suzuki A.( et al.;Ishikawa K.( et al.;Chen GY.( et al.;Lin J.( et al.;Kahn NW.( et al.;Ueno S.( et al.;Fujita M.( et al.;Nakamura M.( et al.;Sato H.( et al.;Nakazawa T.( et al.;Kondo M.( et al.
• 通讯作者: Kondo M.( et al.

Acquired unilateral night blindness : Functional recovery during 10-year follow-up

获得性单侧夜盲症：10 年随访期间功能恢复

• 发表时间: 2005
• 期刊: Retina (in press)
• 作者: Lu W;Ebihara N;Miyazaki K;Murakami A;Kondo M
• 通讯作者: Kondo M