Abstract：
OBJECTIVE: This study aimed to analyze the clinical and genetic characteristics of 6 Chinese patients with foveal hypoplasia (FH) caused by the variants of solute carrier family 38 member 8 (SLC38A8), and to describe the genotype and phenotype of SLC38A8 variants from previous literature.
METHODS: All subjects underwent comprehensive ophthalmic examinations. Optical coherence tomography (OCT) was performed to evaluate the structural grade of FH. Pathogenic variants of SLC38A8 gene were identified using panel-based next-generation sequencing and direct Sanger sequencing techniques. Further, all previously reported cases of SLC38A8 variants were re-analyzed together with the novel ones identified in this study.
RESULTS: Nystagmus and FH were present in 6 patients with variants of SLC38A8 gene, accompanied by a normal anterior segment. Grade 4 FH was identified in 4 patients. A total of 12 variants of SLC38A8 gene were identified, including 9 novel variants. Systematical analysis revealed that half of the variants (30/60) were missense, the majority of which (23/30) were distributed in the transmembrane (TM) domains. Grade 4 FH was detected in the majority of patients (66%, 23/35). There was no statistical difference in the clinical features between the subgroups of patients with 0, 1 and 2 missense variants.
CONCLUSIONS: Severe arrest of foveal development was identified in patients with variants of SLC38A8. This study provides a brief summary of the clinical and genetic characteristics of the pathogenic SLC38A8 variants, which is helpful in the differentiation diagnosis of FH.
METHODS: All subjects underwent comprehensive ophthalmic examinations. Optical coherence tomography (OCT) was performed to evaluate the structural grade of FH. Pathogenic variants of SLC38A8 gene were identified using panel-based next-generation sequencing and direct Sanger sequencing techniques. Further, all previously reported cases of SLC38A8 variants were re-analyzed together with the novel ones identified in this study.
RESULTS: Nystagmus and FH were present in 6 patients with variants of SLC38A8 gene, accompanied by a normal anterior segment. Grade 4 FH was identified in 4 patients. A total of 12 variants of SLC38A8 gene were identified, including 9 novel variants. Systematical analysis revealed that half of the variants (30/60) were missense, the majority of which (23/30) were distributed in the transmembrane (TM) domains. Grade 4 FH was detected in the majority of patients (66%, 23/35). There was no statistical difference in the clinical features between the subgroups of patients with 0, 1 and 2 missense variants.
CONCLUSIONS: Severe arrest of foveal development was identified in patients with variants of SLC38A8. This study provides a brief summary of the clinical and genetic characteristics of the pathogenic SLC38A8 variants, which is helpful in the differentiation diagnosis of FH.
摘要：
目的：本研究旨在分析6例由溶质载体家族38成员8（SLC38A8）变异体引起的中央凹发育不全（FH）的临床和遗传特征，并从以前的文献中描述SLC38A8变体的基因型和表型。
方法：所有受试者都接受了全面的眼科检查。进行光学相干断层扫描（OCT）以评估FH的结构等级。使用基于小组的下一代测序和直接Sanger测序技术鉴定SLC38A8基因的致病变体。Further,之前报道的所有SLC38A8变异病例均与本研究中发现的新病例一起进行了重新分析.
结果：有6例SLC38A8基因变异的患者存在眼球震颤和FH，伴有正常的前节。在4名患者中确定了4级FH。共鉴定出12种SLC38A8基因变异体,包括9种新颖的变体。系统分析显示一半的变异（30/60）是错义的，其中大部分（23/30）分布在跨膜（TM）结构域中。在大多数患者中检测到4级FH(66%，23/35).0、1和2个错义变异的患者亚组之间的临床特点无统计学差别。
结论：在具有SLC38A8变异体的患者中发现了严重的中央凹发育停滞。本研究提供了致病性SLC38A8变异的临床和遗传特征的简要总结，有助于FH的鉴别诊断。
方法：所有受试者都接受了全面的眼科检查。进行光学相干断层扫描（OCT）以评估FH的结构等级。使用基于小组的下一代测序和直接Sanger测序技术鉴定SLC38A8基因的致病变体。Further,之前报道的所有SLC38A8变异病例均与本研究中发现的新病例一起进行了重新分析.
结果：有6例SLC38A8基因变异的患者存在眼球震颤和FH，伴有正常的前节。在4名患者中确定了4级FH。共鉴定出12种SLC38A8基因变异体,包括9种新颖的变体。系统分析显示一半的变异（30/60）是错义的，其中大部分（23/30）分布在跨膜（TM）结构域中。在大多数患者中检测到4级FH(66%，23/35).0、1和2个错义变异的患者亚组之间的临床特点无统计学差别。
结论：在具有SLC38A8变异体的患者中发现了严重的中央凹发育停滞。本研究提供了致病性SLC38A8变异的临床和遗传特征的简要总结，有助于FH的鉴别诊断。
