A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder.
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 disor...
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2021
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oai:doaj.org-article:2f9a3a5365ad4563a237423cdb93c9ca2021-12-02T20:03:18ZA biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder.1553-73901553-740410.1371/journal.pgen.1009803https://doaj.org/article/2f9a3a5365ad4563a237423cdb93c9ca2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009803https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404SNIP1 (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.Zineb AmmousLettie E RawlinsHannah JonesJoseph S LeslieOlivia WengerEthan ScottJim DelineTom HerrRebecca EvansAngela ScheidJoanna KennedyBarry A ChiozaRyan M AmesHarold E CrossErik G PuffenbergerLorna HarriesEmma L BapleAndrew H CrosbyPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 9, p e1009803 (2021) |
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DOAJ |
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Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 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 A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder. |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Zineb Ammous |
| title |
A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder. |
| title_short |
A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder. |
| title_full |
A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder. |
| title_fullStr |
A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder. |
| title_full_unstemmed |
A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder. |
| title_sort |
biallelic snip1 amish founder variant causes a recognizable neurodevelopmental disorder. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/2f9a3a5365ad4563a237423cdb93c9ca |
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