Childhood onset hereditary spastic paraplegia

Gene: KIF1C

Green List (high evidence)

Childhood onset, At least 6 families.

Created: 10 May 2019, 7:17 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 24482476
• 24319291
• 24808017

Variants in this GENE are reported as part of current diagnostic practice

I don't know

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.

Green List (high evidence)

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

Phenotypes
Spastic ataxia 2, autosomal recessive, 611302