The PUF60 gene encodes a ubiquitously expressed essential splicing factor that is recruited to the U2snRNA complex. The complex binds to the 3′ splice site of exons in specific target genes and regulates the inclusion or exclusion of such exons. Recently, pathogenic variants of PUF60 have been shown to cause a relatively specific and potentially recognizable pattern of malformation referred to as Verheij syndrome. Here, we report a 12‐year‐old female patient with a de novo mutation in PUF60 whose phenotype was representative of the milder end of the phenotypic spectrum of Verheij syndrome; the de novo mutation was a frameshift mutation p.(Ser558Cysfs*21) that resulted in the addition of 21 extra amino acids at the carboxy end of the protein. Among the frequent features of Verheij syndrome, the patient exhibited coloboma, cervical spinal segmentation defects, and borderline intellectual functioning, but lacked cardiac abnormalities, deafness, and urogenital abnormalities. The results of RNA analysis using peripheral blood showed the escape of the mutant allele from nonsense‐mediated mRNA decay, possibly accounting for the mild phenotype in the presently reported patient. Based on our clinical observations, we inferred that two embryologic processes, closure of the ocular plate and cervical spinal segmentation, are particularly susceptible to deficient PUF60‐mediated splicing regulation, compared with other embryogenetic processes leading to the central nervous system, heart, ear, and kidney.

中文翻译：

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PUF60的蛋白质延伸变体：Verheij综合征的表型较轻末端。

该PUF60基因编码被招募到U2snRNA复杂的广泛表达必不可少的剪接因子。该复合物结合特定靶基因中外显子的3'剪接位点，并调节此类外显子的包含或排除。最近，PUF60的致病变异体已显示出引起畸形的相对特定且潜在可识别的模式，称为Verheij综合征。在这里，我们报道了一名12岁女性，患有PUF60的从头突变其表型代表Verheij综合征表型谱的较温和末端；从头突变是移码突变p。（Ser558Cysfs * 21），导致在蛋白质的羧基末端添加了21个额外​​的氨基酸。在Verheij综合征的常见特征中，该患者表现出结肠炎，颈椎节段性缺损和边缘性智力功能，但缺乏心脏异常，耳聋和泌尿生殖器异常。使用外周血进行RNA分析的结果表明，突变等位基因逃避了无义介导的mRNA衰变，这可能解释了目前报道的患者的轻度表型。根据我们的临床观察结果，我们推断出两个胚胎学过程，即眼板闭合和颈椎脊髓切开，