Hereditary spastic paraplegia - childhood onset

Gene: LYST

Amber List (moderate evidence)

LYST (lysosomal trafficking regulator)
EnsemblGeneIds (GRCh38): ENSG00000143669
EnsemblGeneIds (GRCh37): ENSG00000143669
OMIM: 606897, Gene2Phenotype
LYST is in 25 panels

4 reviews

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

I don't know

Small number of families with HSP aspect of CHS, childhood and adult onset
Created: 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

Louise Daugherty (Genomics England Curator)

I don't know

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 2018
Created: 2 May 2019, 4:15 p.m.

Publications

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

2 cases reported, family 1- 3 sibs affected with CHS & progressive spastic paraparesis & family2-2pts in consanguinous family. In sheffields HSP panel. Victoria: Green
Created: 28 Apr 2019, 4:16 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
spastic paraplegia; Chediak-Higashi syndrome, 214500

Rebecca Foulger (Genomics England curator)

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.

History Filter Activity

13 May 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to LYST.

2 May 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: lyst has been classified as Amber List (Moderate Evidence).

28 Apr 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: lyst has been classified as Green List (High Evidence).

28 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to LYST.

28 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to LYST.

3 Apr 2019, Gel status: 2

Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

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

28 Jan 2019, Gel status: 2

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Rebecca Foulger: Comment on list classification

8 Jan 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: lyst has been classified as Amber List (Moderate Evidence).

8 Jan 2019, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: LYST were changed from spastic paraplegia to spastic paraplegia; Chediak-Higashi syndrome, 214500

8 Jan 2019, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: LYST were set to 24521565

19 Dec 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Sarah Leigh (Genomics England Curator)

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