Coloboma may be a shared feature in a spectrum of disorders caused by mutations in the WDR37-PACS1-PACS2 axis

Yuri Sakaguchi, Hiroshi Yoshihashi, Tomoko Uehara, Sahoko Miyama, Kenjiro Kosaki, Toshiki Takenouchi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


We report a male adult with early infantile-onset epilepsy, facial dysmorphism, and iridal and choroidal coloboma who had a de novo heterozygous mutation in PACS2, that is, c.625G > A p.(Glu209Lys). This specific mutation was previously reported in a patient with PACS2-related disorder (early infantile epileptic encephalopathy 66). De novo heterozygous mutations in WDR37 have been shown to cause a novel human disorder, neurooculocardiogenitourinary syndrome (NOCGUS syndrome) (OMIM #618652), characterized by intellectual disability, facial dysmorphism, and coloboma. According to large-scale interactome data, WDR37 interacts most strongly, by far, with PACS1 and PACS2. Clinically, coloboma has been described as a feature in a WDR37-related disorder and a PACS1-related disorder (Schuurs-Hoeijmakers syndrome), but not in a PACS2-related disorder. Our review of the phenotypes of three human disorders caused by WDR37, PACS1, and PACS2 mutations showed a significant overlap of epilepsy, intellectual disability, cerebellar atrophy, and facial features. The present observation of coloboma as a shared feature among these three disorders suggests that this group of genes may be involved in ocular development. We propose that dysregulation of the WDR37-PACS1-PACS2 axis results in a spectrum that is recognizable by intellectual disability, distinctive facial features, and coloboma.

Original languageEnglish
Pages (from-to)884-888
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Issue number3
Publication statusPublished - 2021 Mar


  • PACS1
  • PACS2
  • WDR37
  • coloboma
  • intellectual disability

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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