Purpose

To characterize the clinical and genetic features of a Japanese male patient with foveal hypoplasia caused by a homozygous single nucleotide duplication in the SLC38A8 gene.

Methods

We performed a comprehensive ophthalmic examination including full-field electroretinography (FF-ERG) and pattern-reversal visual evoked potentials (PR-VEPs). Whole-exome sequencing (WES) was performed to identify the disease-causing variant; Sanger sequencing was used for confirmation.

Results

In the WES analysis, a homozygous single nucleotide duplication (c.995dupG; p.Trp333MetfsTer35) was identified in SLC38A8 of the patient. His unaffected mother carried the variant heterozygously. The patient exhibited hyperopia, congenital nystagmus, low visual acuity, and grade 4 foveal hypoplasia. Slit-lamp examination revealed mild posterior embryotoxon and goniodysgenesis. Fundus examination revealed the absence of foveal hyperpigmentation and foveal avascularity, but there were no retinal degenerative lesions. In the FF-ERG, the amplitudes of rod ERG, standard-flash, and bright-flash ERG were within the normal range; cone-mediated responses also showed nearly normal amplitudes. The PR-VEP findings revealed delayed P100 latencies and decreased amplitudes of the P100 components, but no chiasmal misrouting.

Conclusions

This report is the first report on the clinical and genetic characteristics of SLC38A8-associated foveal hypoplasia in the Japanese population. This is also the first report of normal rod- and cone-mediated responses in a patient with this disorder.

中文翻译：

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SLC38A8在常染色体隐性中心凹发育不全中的纯合单核苷酸重复：日本首例病例报告

目的

描述一名因SLC38A8基因中的纯合单核苷酸重复而导致中心凹发育不全的日本男性患者的临床和遗传特征。

方法

我们进行了全面的眼科检查，包括全视野视网膜电图 (FF-ERG) 和模式反转视觉诱发电位 (PR-VEP)。进行全外显子组测序 (WES) 以确定致病变异；Sanger测序用于确认。

结果

在 WES 分析中，在患者的SLC38A8中鉴定出纯合单核苷酸重复（c.995dupG；p.Trp333MetfsTer35） 。他未受影响的母亲杂合地携带该变体。患者表现出远视、先天性眼球震颤、视力低下和4级中心凹发育不全。裂隙灯检查显示轻度后胚胎毒素和生殖发育不全。眼底检查显示没有中央凹色素沉着过度和中央凹无血管，但没有视网膜退行性病变。FF-ERG中，视杆ERG、标准闪光、强闪光ERG幅度均在正常范围内；锥介导的反应也显示出几乎正常的幅度。PR-VEP 研究结果显示 P100 延迟延迟和 P100 分量振幅降低，但没有交叉错误路由。

结论

本报告是日本人群中SLC38A8相关中心凹发育不全的临床和遗传特征的第一份报告。这也是该疾病患者正常视杆细胞和视锥细胞介导反应的第一份报告。