Purpose

Thus far, only one Japanese patient with autosomal recessive rod–cone dystrophy (AR-RCD) associated with the phosphodiesterase 6A gene (PDE6A) has been reported. The purpose of this study was to analyze the clinical features of a Japanese female patient with AR-RCD with a novel missense variant in PDE6A.

Methods

We performed whole-exome sequencing (WES) to identify the disease-causing variant and a comprehensive ophthalmic examination including full-field electroretinography (ERG).

Results

WES analysis revealed that the patient carried a novel homozygous missense variant (c.1631G > A; p.Arg544Gln) in PDE6A. Her unaffected parents carried the heterozygous variant. The patient reported night blindness in her early 20 s. At the age of 25 years, she underwent a comprehensive ophthalmic examination. Her corrected visual acuity was 20/13 in the right and 20/10 in the left eyes. Fundus images showed degenerative changes with bone spicule pigmentation in the mid-peripheral retina, and peripheral retinal vessels were not attenuated. Ultra-wide-field fundus autofluorescence images demonstrated large hypoautofluorescent regions corresponding to the degenerative changes, surrounded by hyperautofluorescence. Cross-sectional optical coherence tomography demonstrated a preserved ellipsoid zone and retinal thickness in the center of the macula, with perifoveal atrophy. ERG responses were subnormal, revealing that rod-mediated responses were more affected than cone-mediated responses, consistent with findings observed in RCD.

Conclusions

This is the second case of a patient with AR-RCD associated with PDE6A in the Japanese population. These findings will contribute to a better clinical understanding of PDE6A-associated RCD and valuable insights for gene therapy trials.

中文翻译：

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一种新的 PDE6A 错义变体 p.Arg544Gln 在视杆-视锥细胞营养不良中

目的

迄今为止，仅报道了一名患有与磷酸二酯酶 6A 基因 ( PDE6A ) 相关的常染色体隐性杆锥体营养不良 (AR-RCD) 的日本患者。本研究的目的是分析一名患有PDE6A新型错义变异的日本女性 AR-RCD 患者的临床特征。

方法

我们进行了全外显子组测序 (WES) 以确定致病变异体和全面的眼科检查，包括全视野视网膜电图 (ERG)。

结果

WES 分析显示患者在 PDE6A 中携带一种新的纯合错义变体 (c.1631G > A; p.Arg544Gln ). 她未受影响的父母携带杂合变体。患者在 20 多岁时报告了夜盲症。25 岁时，她接受了全面的眼科检查。她的矫正视力右眼为 20/13，左眼为 20/10。眼底图像显示中周视网膜中骨针状色素沉着的退行性变化，并且周围视网膜血管未衰减。超广角眼底自发荧光图像显示了与退行性变化相对应的大的低自发荧光区域，周围环绕着超自发荧光。横截面光学相干断层扫描显示黄斑中心保留椭圆形区和视网膜厚度，伴有中央凹萎缩。ERG 反应不正常，

结论

这是日本人群中第二例与PDE6A相关的 AR-RCD 患者。这些发现将有助于更好地了解与PDE6A相关的RCD，并为基因治疗试验提供有价值的见解。