The NSUN2 gene encodes a tRNA cytosine methyltransferase that functions in the maturation of leucyl tRNA (Leu) (CAA) precursors, which is crucial for the anticodon‐codon pairing and correct translation of mRNA. Biallelic loss of function variants in NSUN2 are known to cause moderate to severe intellectual disability. Microcephaly, postnatal growth retardation, and dysmorphic facial features are common complications in this genetic disorder, and delayed puberty is occasionally observed. Here, we report four individuals, two sets of siblings, with biallelic loss‐of‐function variants in the NSUN2 gene. The first set of siblings have compound heterozygous frameshift variants: c.546_547insCT, p.Met183Leufs*13; c.1583del, p.Pro528Hisfs*19, and the other siblings carry a homozygous frameshift variant: c.1269dup, p.Val424Cysfs*14. In addition to previously reported clinical features, the first set of siblings showed novel complications of juvenile cataract and chronic nephritis. The other siblings showed hypomyelination and simplified gyral pattern in neuroimaging. NSUN2‐related intellectual disability is a very rare condition, and less than 20 cases have been reported previously. Juvenile cataract, chronic nephritis, and brain anomaly shown in the present patients have not been previously described. Our report suggests clinical diversity of NSUN2‐related intellectual disability.

中文翻译：

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扩大NSUN2基因双等位基因功能丧失变异体的表型：描述四名患有青少年白内障，慢性肾炎或脑部异常的个体为新并发症

所述NSUN2基因编码tRNA的胞嘧啶甲基，在亮氨酰tRNA的（亮氨酸）（CAA）的前体的成熟，这是反密码子密码子配对和mRNA的正确翻译重要的功能。已知NSUN2中双等位基因功能变异的丧失会导致中度至重度智力障碍。小头畸形，产后发育迟缓和面部畸形是这种遗传疾病的常见并发症，偶尔会观察到青春期延迟。在这里，我们报告了4个人，两组兄弟姐妹，在NSUN2中具有双等位基因功能丧失的变异基因。第一组兄弟姐妹具有复合杂合移码变体：c.546_547insCT，p.Met183Leufs * 13；c.1583del，p.Pro528Hisfs * 19和其他兄弟姐妹携带了纯合的移码变体：c.1269dup，p.Val424Cysfs * 14。除了先前报道的临床特征外，第一批兄弟姐妹还表现出少年白内障和慢性肾炎的新并发症。其他兄弟姐妹在神经影像学中显示出髓鞘减少和回旋模式简化。NSUN2相关的智力障碍是一种非常罕见的疾病，以前报道的病例不到20例。先前没有描述本患者中出现的青少年白内障，慢性肾炎和脑部异常。我们的报告建议与NSUN2相关的智力障碍的临床多样性。