Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu city, Shizuoka, 431-3192, Japan.
Jpn J Ophthalmol. 2024 Sep;68(5):401-418. doi: 10.1007/s10384-024-01109-8. Epub 2024 Sep 14.
In today's globalized society, ophthalmologists can examine people of different ethnicities regardless of where they live. The frequency of disease-causing genes varies according to a patient's ethnic background. We explain genetic findings for Japanese patients with inherited eye diseases. Ocular genetics has made great advances over the past 30 years. For example, detecting mutations at nucleotide position 11778 in mitochondrial DNA was useful in the genetic diagnosis of Leber's hereditary optic neuropathy (LHON). I evaluated the genotype-phenotype relationship in cases of corneal dystrophy and inherited retinal dystrophy (IRD). I identified the entire exon sequence of the eyes shut homolog (EYS) gene in patients with autosomal recessive retinitis pigmentosa (RP). EYS gene mutations are the most frequent cause of autosomal recessive RP. RPGRIP1 may be a common causative gene with early-onset severe retinal dystrophy, including Leber congenital amaurosis. However, some genes have complex structures that are difficult to analyze, including the OPN1LW/OPN1MW gene cluster in blue cone monochromacy and the IKBKG/NEMO genes in incontinentia pigmenti. This review will also present two cases with uniparental disomy, a case of IRD with double mutations, and a case with RP complicated with LHON-like neuropathy. Precise understanding of the effects of genetic variants may reveal differences in the clinical characteristics of patients with the same variant. When starting genome medicine, accurately diagnosing the patient, making accurate prediction, determining the genetic pattern, and providing genetic counseling are important. Above all, that both the doctors and patients understand genetic diseases correctly is important.
在当今全球化的社会中,眼科医生可以为不同种族的人进行检查,无论他们居住在哪里。致病基因的频率因患者的种族背景而异。我们对日本遗传性眼病患者的遗传发现进行了解释。眼科学在过去 30 年中取得了巨大的进展。例如,检测线粒体 DNA 核苷酸位置 11778 的突变在莱伯遗传性视神经病变(LHON)的遗传诊断中非常有用。我评估了角膜营养不良和遗传性视网膜病变(IRD)的基因型-表型关系。我在常染色体隐性视网膜色素变性(RP)患者中鉴定了眼睛关闭同源物(EYS)基因的整个外显子序列。EYS 基因突变是常染色体隐性 RP 的最常见原因。RPGRIP1 可能是一种常见的致病基因,与包括莱伯先天性黑矇在内的早发性严重视网膜营养不良有关。然而,一些基因具有复杂的结构,难以分析,包括蓝色锥体单色性中的 OPN1LW/OPN1MW 基因簇和 incontinentia pigmenti 中的 IKBKG/NEMO 基因。本综述还将介绍两例单亲二体性病例、一例具有双重突变的 IRD 病例和一例伴有 LHON 样神经病的 RP 病例。对遗传变异影响的精确理解可能揭示出具有相同变异的患者在临床特征上的差异。当启动基因组医学时,准确诊断患者、进行准确预测、确定遗传模式和提供遗传咨询非常重要。最重要的是,医生和患者都要正确理解遗传疾病。