論文

査読有り 国際誌
2020年8月27日

Protein elongation variant of PUF60: Milder phenotypic end of the Verheij syndrome.

American journal of medical genetics. Part A
  • Mamiko Yamada
  • ,
  • Tomoko Uehara
  • ,
  • Hisato Suzuki
  • ,
  • Toshiki Takenouchi
  • ,
  • Kenjiro Kosaki

記述言語
英語
掲載種別
DOI
10.1002/ajmg.a.61816

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.

リンク情報
DOI
https://doi.org/10.1002/ajmg.a.61816
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32851780

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