Childhood onset hereditary spastic paraplegia

Gene: LYST

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

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

• 25519960
• 25519961
• 24521565
• 26307451
• 25519960
• 25519961

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

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.