Novel pathogenic variants of SLC38A8 gene and literature review

Abstract

Abstract Purpose This study aimed to analyze the clinical and genetic characteristics of 6 Chinese Han patients with foveal hypoplasia (FH) caused by the variants of solute carrier family 38 member 8 (SLC38A8) gene, and to describe the genotype and phenotype of SLC38A8 gene variants from previous literature. Methods All subjects underwent comprehensive ophthalmic examinations including slit lamp microscope, fundoscopy, and retinoscopy refraction. Optical coherence tomography (OCT) was performed to evaluate the structural grade of foveal hypoplasia. Pathogenic variants of SLC38A8 gene were identified using panel-based next-generation sequencing, direct Sanger sequencing, and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) 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 who could cooperate with the OCT scan. A total of 12 variants of SLC38A8 gene were identified, including 9 novel variants. The missense variants were predicted to be pathogenic by the online programs. Systematical analysis revealed that half of the variants (30/60) were missense, and 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), and anterior segment dysgenesis (ASD)was found in 16.5% of patients (15/91). There was no statistical difference in the clinical features between the subgroups of patients with 0, 1 and 2 missense variants. Conclusion Severe arrest of foveal development was identified in patients with variants of SLC38A8. The novel identified variants may expand the spectrum of pathogenic variants of SLC38A8. This study summarized the phenotypic and genotypic characteristics of SLC38A8variants, which would help the FH patients with early diagnosis.