Childhood onset hereditary spastic paraplegia
Gene: LYST
Small number of families with HSP aspect of CHS, childhood and adult onsetCreated: 9 May 2019, 6:14 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Variants in this GENE are reported as part of current diagnostic practice
Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber 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
Comment on publications: PMIDs:25519960 and 25519961 are in Japanese.
Rebecca Foulger (Genomics England curator), 8 Jan 2019
Comment on list classification: Updated rating from Red to Amber. Gene added to panel by Chris Buxton (Bristol NHS) based on one family in PMID:24521565. In addition, progressive spastic paraparesis seen in affected siblings in PMID:26307451, and PMIDs 25519960 and 25519961 describe LYST as a potential HSP locus. Further cases required for a diagnostic rating.
Rebecca Foulger (Genomics England curator), 8 Jan 2019
PMID:26307451 (Desai et al 2016) report 3 affected siblings with the late-onset form of CHS, and phenotypes including progressive spastic paraparesis.
Rebecca Foulger (Genomics England curator), 8 Jan 2019
PMID:24521565 (Shimazaki et al 2014) include 2 patients in a Japanese family with parents who are first cousins. They detected a homozygous missense variant (c.4189T>G, p.F1397V) in the LYST gene. The patients had adult Chediak-Higashi syndrome (CHS) presenting spastic paraplegia with cerebellar ataxia and neuropathy.
Rebecca Foulger (Genomics England curator), 8 Jan 2019
Comment on list classification: This gene is awaiting curator evaluation and rating.
Sarah Leigh (Genomics England Curator), 19 Dec 2018
Shimazaki (2014, 24521565), homozygous LYST (c.4189T>G, p.F1397V). Gene predominantly associated with Chediak-Higashi syndrome. one publication describing a HSP like phenotype. Diagnostic on Sheffield HSP panel Sources: Literature
Chris Buxton (North Bristol NHS Trust), 28 Nov 2018Created: 2 May 2019, 4:15 p.m.
Publications
2 cases reported, family 1- 3 sibs affected with CHS & progressive spastic paraparesis & family2-2pts in consanguinous family. In sheffields HSP panel. Victoria: GreenCreated: 28 Apr 2019, 4:16 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
spastic paraplegia; Chediak-Higashi syndrome, 214500
Comment on list classification: Updated rating from Red to Amber following review on the Hereditary spastic paraplegia panel.Created: 8 Jan 2019, 3:45 p.m.
Source Yorkshire and North East GLH was added to LYST.
Gene: lyst has been classified as Amber List (Moderate Evidence).
Gene: lyst has been classified as Green List (High Evidence).
Source NHS GMS was added to LYST.
Source London North GLH was added to LYST.
Added phenotypes spastic paraplegia; Chediak-Higashi syndrome, 214500 for gene: LYST Publications for gene LYST were changed from 24521565; 26307451; 25519960; 25519961 to 24521565; 26307451; 25519961; 25519960
Rebecca Foulger: Comment on list classification
Gene: lyst has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: LYST were changed from spastic paraplegia to spastic paraplegia; Chediak-Higashi syndrome, 214500
Publications for gene: LYST were set to 24521565
gene: LYST was added gene: LYST was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Red,Literature Mode of inheritance for gene: LYST was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LYST were set to 24521565 Phenotypes for gene: LYST were set to spastic paraplegia