Hereditary spastic paraplegia

Gene: DARS

Amber List (moderate evidence)

DARS (aspartyl-tRNA synthetase)
EnsemblGeneIds (GRCh38): ENSG00000115866
EnsemblGeneIds (GRCh37): ENSG00000115866
OMIM: 603084, Gene2Phenotype
DARS is in 15 panels

4 reviews

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: 1.205
Gene to be reviewed again after the GMS Neurology specialist test group have reviewed and agreed rating of gene on the Hereditary spastic paraplegia - childhood onset panel on May 2019
Created: 3 May 2019, 8:27 a.m.

Rebecca Foulger (Genomics England curator)

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.
Created: 8 Jan 2019, 1:53 p.m.
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.
Created: 8 Jan 2019, 1:50 p.m.

Sarah Leigh (Genomics England Curator)

Comment on list classification: This gene is awaiting curator evaluation and rating.
Created: 19 Dec 2018, 2:11 p.m.

Chris Buxton (North Bristol NHS Trust)

I don't know

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
Created: 28 Nov 2018, 10:28 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Brain stem and spinal cord Hypomyelination; leg spasticity

Publications

History Filter Activity

6 Sep 2019, Gel status: 2

Added Tag

Louise Daugherty (Genomics England Curator)

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

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 Brain stem and spinal cord Hypomyelination; leg spasticity 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

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: dars has been classified as Red List (Low Evidence).

28 Nov 2018, Gel status: 0

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

Chris Buxton (North Bristol NHS Trust)

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