Homozygous single nucleotide duplication of SLC38A8 in autosomal recessive foveal hypoplasia: The first Japanese case report
Homozygous single nucleotide duplication of SLC38A8 in autosomal recessive foveal hypoplasia: The first Japanese case report
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DOI：
10.1007/s10633-021-09842-y
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发表时间：
2021-05-26
影响因子：
1.4
通讯作者：
Nakano, Tadashi
中科院分区：
文献类型：
--
作者：
Hayashi, Takaaki;Kondo, Hiroyuki;Nakano, Tadashi
目的探讨1例由SLC38A8基因纯合单核苷酸重复引起的日本男性中央凹发育不全患者的临床和遗传学特征。方法采用全视场视网膜电图（FF-ERG）和模式反转视觉诱发电位（PR-VEPs）进行全面眼科检查。采用全外显子组测序（WES）鉴定致病变异；采用Sanger测序进行确认。结果在患者的SLC38A8基因中检测到一个纯合单核苷酸重复（c.995dupG; p.Trp333MetfsTer35）。他未受影响的母亲杂合携带了这种变体。患者表现为远视、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后胚缩和性腺发育。眼底检查未见中央凹色素沉着，中央凹无血管，未见视网膜退行性病变。FF-ERG中杆状ERG、标准闪光ERG、亮闪光ERG幅值均在正常范围内；锥体介导的反应也显示出接近正常的振幅。PR-VEP结果显示P100潜伏期延迟和P100组分振幅下降，但没有交叉错路。本报告首次报道了日本人群slc38a8相关的中央凹发育不全的临床和遗传特征。这也是第一次报道正常的杆状和锥体介导的反应在患者的这种疾病。
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.