Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
Retina. 2024 Oct 1;44(10):1836-1844. doi: 10.1097/IAE.0000000000004170.
To ascertain the characteristics of achromatopsia (ACHM) in Japan by analyzing the genetic and phenotypic features of patients with ACHM.
The medical records of 52 patients from 47 Japanese families who were clinically diagnosed with ACHM were reviewed in this retrospective observational study.
Thirty-six causative variants of ACHM were identified in 26 families via whole-exome sequencing: PDE6C (12 families), CNGA3 (10 families), CNGB3 (two families), and GNAT2 (two families). However, none of the 6 causative variants that are known to cause ACHM, or the 275 other genes listed in RetNet, were observed in 19 families. A significant trend toward older age and worsening of ellipsoid zone disruption on optical coherence tomography images was observed (P < 0.01). Progressive ellipsoid zone disruptions were observed in 13 eyes of seven patients during the follow-up visits. These patients harbored one or more variants in PDE6C.
The ACHM phenotype observed in this study was similar to those observed in previous reports; however, the causative gene variants differed from those in Europe. The low identification ratio of causative genes in whole-exome sequencing suggests the presence of unique hotspots in Japanese patients with ACHM that were not detectable via ordinal whole-exome sequencing.
通过分析先天性静止性夜盲症（ACHM）患者的遗传和表型特征，确定日本 ACHM 的特征。
本回顾性观察研究分析了 47 个日本家族的 52 名临床诊断为 ACHM 患者的病历。
通过全外显子组测序，在 26 个家族中发现了 36 个 ACHM 的致病变异：PDE6C（12 个家族）、CNGA3（10 个家族）、CNGB3（2 个家族）和 GNAT2（2 个家族）。然而，在 19 个家族中未观察到已知导致 ACHM 的 6 个致病变异或 RetNet 中列出的 275 个其他基因。观察到年龄较大和光相干断层扫描图像上椭圆体带破坏恶化的显著趋势（P<0.01）。在 7 名患者的 13 只眼中观察到进行性椭圆体带破坏。这些患者在 PDE6C 中携带一个或多个变异。
本研究观察到的 ACHM 表型与以往报告相似，但致病基因变异与欧洲不同。全外显子组测序中致病基因的低鉴定率表明，日本 ACHM 患者存在独特的热点，通过常规全外显子组测序无法检测到。
