Childhood onset hereditary spastic paraplegia
Gene: NSRP1
The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 2:55 p.m. | Last Modified: 1 Feb 2023, 2:55 p.m.
Panel Version: 3.9
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 2:55 p.m. | Last Modified: 1 Feb 2023, 2:55 p.m.
Panel Version: 3.9
Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote to Green at the next GMS panel update.
The NSRP1 gene is not yet associated with any phenotype in OMIM but has a 'strong' disease confidence rating in G2P for 'NSRP1-associated developmental delay, epilepsy and microcephaly'.
Six individuals from three families with different homozygous LoF NSRP1 variants identified by Calame et al. 2021 (PMID: 34385670). Main clinical features include ID/DD (6/6), epilepsy (6/6, drug-resistant in 3/6), hypotonia (6/6), appendicular spasticity (6/6), microcephaly (5/6, Z-scores −0.95 to −5.60). Brain abnormalities included under-opercularization (3/4), simplified gyral pattern (3/4), superior and/or inferior cerebellar vermian hypoplasia (3/4), corpus callosum dysgenesis (1/4), and thin brainstem (1/4).Created: 1 Aug 2022, 11:24 a.m. | Last Modified: 1 Aug 2022, 11:24 a.m.
Panel Version: 3.1641
Novel gene regulating splicing. Biallelic LoF pathogenic variants reported in 6 individuals from 3 unrelated families associated with a phenotype characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.
Sources: LiteratureCreated: 4 Dec 2021, 7:47 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Epilepsy; Cerebral palsy; microcephaly; Intellectual disability
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q3_22_rating was removed from gene: NSRP1.
Source Expert Review Green was added to NSRP1. Source NHS GMS was added to NSRP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: NSRP1 was added gene: NSRP1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Amber,Literature Q3_22_rating tags were added to gene: NSRP1. Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NSRP1 were set to 34385670 Phenotypes for gene: NSRP1 were set to NSRP1-associated developmental delay, epilepsy and microcephaly