Hereditary spastic paraplegia
Gene: KIDINS220Comment on mode of pathogenicity: Personal communication from Dmitrijs Rots (RadboudUMC). Prompted by the occurrence of a KIDINS220 nonsense variant in the middle of the gene, in a family without spastic paraplegia (HSP) or other features; an in-depth analysis of KIDINS220 variants was performed. It would appear that KIDINS220 gene is tolerant of LOF variants (nonsense, frameshift) in gnomAD population (hence pLI~ 0, in the PanelApp review by Dmitrijs Rots (RadboudUMC), 4 Nov 2021). This was unexpected, as KIDINS220-associated-HSP presents in childhood, so it would appear that haploinsufficiency is unlikely as the mechanism. In addition, there were nonsense/frameshift HSP-associated variants in KIDINS220, but they were located in the last two exons of the gene and so likely to escape nonsense mediated decay. Therefore, it is proposed that rather a LOF mechanism a dominant negative effect may be responsible, however, further cases need to be identified to confirm this.Created: 18 Nov 2021, 4:11 p.m. | Last Modified: 18 Nov 2021, 4:11 p.m.
Panel Version: 1.272
Additional family reported in PMID: 33763417.
All reported pathogenic variants seems to locate in the last two exons, as well as pLI is ~0, so could be dominant negative ?Created: 4 Nov 2021, 10:45 a.m. | Last Modified: 4 Nov 2021, 10:45 a.m.
Panel Version: 1.259
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Spastic paraplegia; intellectual disability
Publications
Mode of pathogenicity
Other
Three unrelated cases presenting with ID, spasticity and other variable features.Created: 2 Jan 2018, 3:26 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Spastic paraplegia, intellectual disability, nystagmus, and obesity 617296
Mode of pathogenicity for gene: KIDINS220 was changed from None to None
Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity 617296 to Spastic paraplegia, intellectual disability, nystagmus, and obesity OMIM:617296
Publications for gene: KIDINS220 were set to 27005418; 29667355; 31630374
Publications for gene: KIDINS220 were set to
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
KIDINS220 was added to Hereditary spastic paraplegia panel. Sources: Other
KIDINS220 was created by Helen Brittain