Abstract：
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.
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.
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.
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.
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.
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.
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.
摘要：
目的表征日本男性患者的临床和遗传特征，该患者患有由SLC38A8基因中的纯合单核苷酸重复引起的中央凹发育不全。
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)以鉴定致病变体;Sanger测序用于确认。
在WES分析中，在患者的SLC38A8中鉴定出纯合的单核苷酸重复(c.995dupG;p.Trp333MetfsTer35)。他未受影响的母亲杂合地携带了变体。患者表现出远视，先天性眼球震颤,低视力，和4级中央凹发育不全。裂隙灯检查显示轻度的后部胚胎毒素和性腺发育。眼底检查显示没有中央凹色素沉着过度和中央凹无血管，但没有视网膜变性病变.在FF-ERG中,杆ERG的振幅，标准闪光灯，和亮闪ERG在正常范围内;视锥介导的反应也显示出接近正常的振幅。PR-VEP的发现揭示了P100延迟和P100成分的振幅降低，但没有破烂的路线。
本报告是关于日本人群SLC38A8相关中央凹发育不全的临床和遗传特征的第一份报告。这也是患有这种疾病的患者的正常杆和锥介导的反应的首次报道。
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)以鉴定致病变体;Sanger测序用于确认。
在WES分析中，在患者的SLC38A8中鉴定出纯合的单核苷酸重复(c.995dupG;p.Trp333MetfsTer35)。他未受影响的母亲杂合地携带了变体。患者表现出远视，先天性眼球震颤,低视力，和4级中央凹发育不全。裂隙灯检查显示轻度的后部胚胎毒素和性腺发育。眼底检查显示没有中央凹色素沉着过度和中央凹无血管，但没有视网膜变性病变.在FF-ERG中,杆ERG的振幅，标准闪光灯，和亮闪ERG在正常范围内;视锥介导的反应也显示出接近正常的振幅。PR-VEP的发现揭示了P100延迟和P100成分的振幅降低，但没有破烂的路线。
本报告是关于日本人群SLC38A8相关中央凹发育不全的临床和遗传特征的第一份报告。这也是患有这种疾病的患者的正常杆和锥介导的反应的首次报道。
