Hereditary spastic paraplegia - childhood onset

Gene: DARS

Green List (high evidence)

DARS (aspartyl-tRNA synthetase)
EnsemblGeneIds (GRCh38): ENSG00000115866
EnsemblGeneIds (GRCh37): ENSG00000115866
OMIM: 603084, Gene2Phenotype
DARS is in 16 panels

4 reviews

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

Green List (high evidence)

Childhood and adult onset. Spasticity usually part of wider syndrome but cases exist as initial presentation.
Created: 9 May 2019, 11:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Louise Daugherty (Genomics England Curator)

I don't know

Added new-gene-name tag, new approved HGNC gene symbol for DARS is DARS1
Created: 6 Sep 2019, 11:38 a.m. | Last Modified: 6 Sep 2019, 11:38 a.m.
Panel Version: 1.178
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.
Comment on list classification: Updated rating from Red to Amber to match expert review and literature evidence. Added to panel and rated Amber by Chris Buxton (Bristol NHS). 2 patients in PMID:25527264 with onset in late adolescence who presented with subacute spastic paraplegia.
Rebecca Foulger (Genomics England curator), 8 Jan 2019

Wolf (2015, 25527264) report 3 patients with variants in DARS. One patient had typical infantile presentation but 2 patients with onset in late adolescence presented with subacute spastic paraplegia. Patient 1 was compound heterozygous for c.599C>G; p.Ser200Cys and c.830C>T; p.Ser277Phe. Patient 2 was homozygous for c.1277T>C; p.Leu426Ser, and patient 3 compound heterozygous for c.839A>T; p.His280Leu and c.1099G>C; p.Asp367His.
Rebecca Foulger (Genomics England curator), 8 Jan 2019

Amber rating on Hereditary spastic paraplegia panel 1.198

Comment on list classification: This gene is awaiting curator evaluation and rating.
Sarah Leigh (Genomics England Curator), 19 Dec 2018

HGMD: 15 missense, 1 ins associated with: Hypomyelination with brain stem and spinal cord involvement and leg spasticity: An autosomal recessive leukoencephalopathy characterized by onset in the first year of life of severe spasticity, mainly affecting the lower limbs and resulting in an inability to achieve independent ambulation Taft (2013, 23643384) identiofied compound-heterozygous and homozygous DARS missense variants in 7 unrelated families with severe lower limb spasticity associated with leukoencephalopathy Phenotype expanded by Wolf (2015, 25527264) to later onset and subacute spastic paraplegia. Sources: Literature
Chris Buxton (North Bristol NHS Trust), 28 Nov 2018
Created: 2 May 2019, 3:52 p.m.

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

Green List (high evidence)

10 patients from 7 unrelated families of various origins with hypomyelination with brainstem and spinal cord involvement and spasticity
Created: 28 Apr 2019, 4:16 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Brain stem and spinal cord Hypomyelination; leg spasticity; Hypomyelination with brainstem and spinal cord involvement and leg spasticity, 615281

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, 1:55 p.m.

History Filter Activity

6 Sep 2019, Gel status: 3

Added Tag

Louise Daugherty (Genomics England Curator)

Tag new-gene-name tag was added to gene: DARS.

21 May 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to DARS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

13 May 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to DARS.

2 May 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: dars 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: dars 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 DARS.

28 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to DARS.

3 Apr 2019, Gel status: 2

Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Added phenotypes leg spasticity; Brain stem and spinal cord Hypomyelination; Hypomyelination with brainstem and spinal cord involvement and leg spasticity, 615281 for gene: DARS Publications for gene DARS were changed from 25527264; 23643384 to 23643384; 25527264

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

8 Jan 2019, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: DARS were changed from leg spasticity; Brain stem and spinal cord Hypomyelination to Brain stem and spinal cord Hypomyelination; leg spasticity; Hypomyelination with brainstem and spinal cord involvement and leg spasticity, 615281

19 Dec 2018, Gel status: 1

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

Sarah Leigh (Genomics England Curator)

gene: DARS was added gene: DARS was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Red,Literature Mode of inheritance for gene: DARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DARS were set to 25527264; 23643384 Phenotypes for gene: DARS were set to leg spasticity; Brain stem and spinal cord Hypomyelination