NSRP1 was first reported in relation to autosomal recessive neurodevelopmental disorder with spasticity, seizures, and brain abnormalities in 2021 (Calame et al., PMID: 34385670). Individuals with variants in NSRP1 can present with features such as global developmental delay apparent in infancy, axial hypotonia, peripheral spasticity, and early-onset seizures of various types and severity. Other phenotypes can include delayed walking or inability to walk and impaired intellectual development with poor or absent speech.
Five variants (frameshift, nonsense,missense) that have been reported in 4 probands in 2 publications (PMIDs: 34385670, 38808951) are included in this curation. The mechanism of pathogenicity is reported to be loss of function (PMID: 34385670).
In summary, there is moderate evidence to support this gene-disease relationship between NSRP1 and autosomal recessive neurodevelopmental disorder with spasticity, seizures, and brain abnormalities. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has been reported. This classification was approved by the ClinGen Cerebral Palsy Gene Curation Expert Panel on December 16, 2024 (SOP Version 11).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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