In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2021-9-27), p. e1009803-
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.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1009803
DOI:
10.1371/journal.pgen.1009803.g001
DOI:
10.1371/journal.pgen.1009803.t001
DOI:
10.1371/journal.pgen.1009803.t002
DOI:
10.1371/journal.pgen.1009803.t003
DOI:
10.1371/journal.pgen.1009803.s001
DOI:
10.1371/journal.pgen.1009803.s002
DOI:
10.1371/journal.pgen.1009803.s003
DOI:
10.1371/journal.pgen.1009803.s004
DOI:
10.1371/journal.pgen.1009803.s005
DOI:
10.1371/journal.pgen.1009803.s006
DOI:
10.1371/journal.pgen.1009803.s007
DOI:
10.1371/journal.pgen.1009803.s008
DOI:
10.1371/journal.pgen.1009803.s009
DOI:
10.1371/journal.pgen.1009803.r001
DOI:
10.1371/journal.pgen.1009803.r002
DOI:
10.1371/journal.pgen.1009803.r003
DOI:
10.1371/journal.pgen.1009803.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2186725-2
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