Hereditary spastic paraplegia - childhood onsetGene: KIF1C
Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Created: 21 May 2019, 4:50 p.m.
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 4:54 p.m.
Amber rating on Hereditary spastic paraplegia panel 1.198
More familailes listed on OMIM (Nov 2018): In affected members of 2 unrelated families with SPAX2, Dor et al. (2014) identified 2 different homozygous mutations in the KIF1C gene (R731X, 603060.0001 and R169W, 603060.0002). The mutations were found using a combination of homozygosity mapping and whole-exome sequencing. Functional studies were not performed. In 2 consanguineous families with SPAX2, Novarino et al. (2014) identified homozygous mutations in the KIF1C gene: the R731X mutation previously identified by Dor et al. (2014) and a splice site mutation (603060.0003). Novarino et al. (2014) also identified a homozygous deletion of exons 14-18 of the KIF1C gene (603060.0004) in affected members of the Moroccan family with SPAX2 reported by Bouslam et al. (2007).
Chris Buxton (North Bristol NHS Trust), 26 Nov 2018 Amber rating submitted
One patient in Gel cohort found to have compound heterozygous VUS but uncertain significance. To review literature when panel next reviewed
Alice Gardham (Genomics England), 19 Jan 2017
Comment when marking as ready: Still only limited evidence
emma baple (Genomics England Curator), 10 May 2016
Created: 2 May 2019, 4:12 p.m.
in liturature: affected members of 2 unrelated families-cerebellar ataxia and variable spasticity of the lower limbs. In sheffield HSP panel
Created: 28 Apr 2019, 4:16 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Spastic ataxia 2, autosomal recessive, 611302
Source Expert Review Green was added to KIF1C. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Source Yorkshire and North East GLH was added to KIF1C.
Gene: kif1c has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: KIF1C were changed from Spastic ataxia 2,autosomal recessive to Spastic ataxia 2, autosomal recessive, 611302
Gene: kif1c has been classified as Green List (High Evidence).
Source NHS GMS was added to KIF1C.
Source London North GLH was added to KIF1C.
Added phenotypes Spastic ataxia 2,autosomal recessive for gene: KIF1C Publications for gene KIF1C were changed from 17273843; 24482476; 24319291 to 24482476; 17273843; 24319291
Rebecca Foulger: Comment on list classification
gene: KIF1C was added gene: KIF1C was added to Hereditary spastic paraplegia - childhood onset. Sources: Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red Mode of inheritance for gene: KIF1C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF1C were set to 17273843; 24482476; 24319291 Phenotypes for gene: KIF1C were set to Spastic ataxia 2,autosomal recessive