PURPOSE A recently described subtype of foveal hypoplasia with congenital nystagmus and optic-nerve-decussation defects was found to be associated with mutations in the SLC38A8 gene. The aim of this study is to advance the clinical and molecular knowledge of SLC38A8 gene mutations. METHODS Five Israeli families with congenital foveal hypoplasia were studied, two of Karait Jewish origins and three of Indian Jewish origins. Subjects underwent a comprehensive ophthalmic examination including retinal photography and ocular coherence tomography. Molecular analysis including whole exome sequencing and screening of the SLC38A8 gene for specific disease-causing variants was performed. RESULTS Eight affected individuals were identified, all had congenital nystagmus and all but one had hypoplastic foveal pits. Anterior segment dysgenesis was observed in only one patient, one had evidence of developmental delay and another displayed early age-related macular degeneration (AMD). Molecular analysis revealed a recently described homozygous mutation, c.95T > G; p.Ile32Ser, in two families of Jewish Indian descent, and the same mutation in two families of Karaite Jewish descent. In a patient with only one pathogenic mutation (c.95T > G; p.Ile32Ser), a possible partial clinical expression of the disorder was seen. One patient of Jewish Indian descent was found to be compound heterozygous for c.95T > G; p.Ile32Ser and a novel mutation c.490_491delCT; p.L164Vfs*41. CONCLUSIONS In five unrelated families with congenital nystagmus and foveal hypoplasia, mutations in the SLC38A8 gene were identified. Possible partial expression in a heterozygous patient was observed and novel potential disease-related phenotypes were identified including early-onset AMD and developmental delay. A novel mutation was also identified and a similar mutation in both Indian and Karaite Jewish ethnicities could be suggestive for common ancestry.

中文翻译：

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SLC38A8在五个患有中央凹发育不全和先天性眼球震颤的家庭中的致病性。

目的发现最近描述的伴有先天性眼球震颤和视神经病变缺陷的中央凹发育不全的亚型与SLC38A8基因的突变有关。这项研究的目的是提高SLC38A8基因突变的临床和分子知识。方法研究了五个以色列人先天性中央凹发育不全的家庭，其中两个是卡拉伊特犹太人血统，三个是印度犹太人血统。受试者接受了全面的眼科检查，包括视网膜摄影和眼科断层扫描。进行了分子分析，包括整个外显子组测序和筛选SLC38A8基因的特定致病变异。结果确定了八名受影响的个体，均患有先天性眼球震颤，除一名以外，其余均患有发育不良的中央凹坑。仅在一名患者中观察到前节发育不全，一名有发育迟缓的证据，​​另一名表现出与年龄有关的早期黄斑变性（AMD）。分子分析显示最近描述的纯合突变，c.95T> G；p.Ile32Ser，在两个印度裔犹太人血统家族中，并且在两个家庭中在Karaite犹太人血统家族中具有相同的突变。在只有一个病原性突变（c.95T> G； p.Ile32Ser）的患者中，发现该疾病可能是部分临床表达。发现一名犹太裔印度裔患者的c.95T> G为复合杂合型；p.Ile32Ser和一个新的突变c.490_491delCT；第L164Vfs * 41页 结论在五个不相关的先天性眼球震颤和中央凹发育不全的家庭中，鉴定出SLC38A8基因突变。观察到在杂合患者中可能的部分表达，并鉴定了与疾病相关的新潜在表型，包括早期发作的AMD和发育延迟。还发现了一个新的突变，在印度和卡拉伊特犹太人种族中类似的突变可能暗示着共同的血统。