A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder

Zineb Ammous, Lettie E. Rawlins, Hannah Jones, Joseph S. Leslie, Olivia Wenger, Ethan Scott, Jim Deline, Tom Herr, Rebecca Evans, Angela Scheid, Joanna Kennedy, Barry A. Chioza, Ryan M. Ames, Harold E. Cross, Erik G. Puffenberger, Lorna Harries, Emma L. Baple, Andrew H. Crosby

Research output: Contribution to journalArticlepeer-review

Abstract

SNIP1 (Smad nuclear interacting protein 1) is a widely expressed transcriptional suppressor of the TGF-β signal-transduction pathway which plays a key role in human spliceosome function. Here, we describe extensive genetic studies and clinical findings of a complex inherited neurodevelopmental disorder in 35 individuals associated with a SNIP1 NM_024700.4:c.1097A>G, p.(Glu366Gly) variant, present at high frequency in the Amish community. The cardinal clinical features of the condition include hypotonia, global developmental delay, intellectual disability, seizures, and a characteristic craniofacial appearance. Our gene transcript studies in affected individuals define altered gene expression profiles of a number of molecules with well-defined neurodevelopmental and neuropathological roles, potentially explaining clinical outcomes. Together these data confirm this SNIP1 gene variant as a cause of an autosomal recessive complex neurodevelopmental disorder and provide important insight into the molecular roles of SNIP1, which likely explain the cardinal clinical outcomes in affected individuals, defining potential therapeutic avenues for future research.

Original languageEnglish (US)
Article numbere1009803
JournalPLoS genetics
Volume17
Issue number9
DOIs
StatePublished - Sep 27 2021

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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