SCYL1 disease results from biallelic pathogenic variants in SCYL1. We report two new patients with severe hepatic phenotype requiring liver transplantation. Patient charts reviewed. DNA samples and skin fibroblasts were utilized. Literature was reviewed. 13‐year‐old boy and 9‐year‐old girl siblings had acute liver insufficiency and underwent living related donor liver transplantation in infancy with no genetic diagnosis. Both had tremor, global developmental delay, and cognitive dysfunction during their follow‐up in the medical genetic clinic for diagnostic investigations after their liver transplantation. Exome sequencing identified a likely pathogenic variant (c.399delC; p.Asn133Lysfs*136) in SCYL1. Deletion/duplication analysis of SCYL1 identified deletions of exons 7–8 in Patient 1. Both variants were confirmed in Patient 2 and the diagnosis of SCYL1 disease was confirmed in both patients at the age of 13 and 9 years, respectively. SCYL1 protein was not expressed in both patients' fibroblast using western blot analysis. Sixteen patients with SCYL1 disease reported in the literature. Liver phenotype (n = 16), neurological phenotype (n = 13) and skeletal phenotype (n = 11) were present. Both siblings required liver transplantation in infancy and had variable phenotypes. Exome sequencing may miss the diagnosis and phenotyping of patients can help to diagnose patients.

中文翻译：

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通过外显子组测序和 SCYL1 缺失/重复分析的再分析诊断 SCYL1 疾病和肝移植

SCYL1疾病由SCYL1中的双等位基因致病变异引起。我们报告了两名需要肝移植的严重肝表型新患者。患者图表审查。使用了 DNA 样品和皮肤成纤维细胞。文献进行了审查。13 岁男孩和 9 岁女孩兄弟姐妹患有急性肝功能不全，并在没有遗传诊断的婴儿时期接受了活体相关供体肝移植。在肝移植后在医学遗传诊所进行诊断调查期间，两人都出现了震颤、全面发育迟缓和认知功能障碍。外显子测序确定了可能的致病变种（c.399delC; p.Asn133Lysfs * 136）在SCYL1。SCYL1 的删除/重复分析在患者 1 中发现了外显子 7-8 的缺失。在患者 2 中确认了这两种变异，并且分别在 13 岁和 9 岁时在两名患者中确认了SCYL1疾病的诊断。使用蛋白质印迹分析，SCYL1 蛋白在两名患者的成纤维细胞中均未表达。文献中报道了16 名SCYL1疾病患者。存在肝脏表型 ( n = 16)、神经表型 ( n = 13) 和骨骼表型 ( n = 11)。两个兄弟姐妹在婴儿期都需要肝移植，并且有不同的表型。外显子组测序可能会漏诊，而患者的表型分析有助于诊断患者。