Childhood onset hereditary spastic paraplegia
Gene: DARS
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
Added new-gene-name tag, new approved HGNC gene symbol for DARS is DARS1Created: 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 2018Created: 2 May 2019, 3:52 p.m.
10 patients from 7 unrelated families of various origins with hypomyelination with brainstem and spinal cord involvement and spasticityCreated: 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
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.
Tag new-gene-name tag was added to gene: DARS.
Source Expert Review Green was added to DARS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Source Yorkshire and North East GLH was added to DARS.
Gene: dars has been classified as Amber List (Moderate Evidence).
Gene: dars has been classified as Green List (High Evidence).
Source NHS GMS was added to DARS.
Source London North GLH was added to DARS.
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
Rebecca Foulger: Comment on list classification
Gene: dars has been classified as Amber List (Moderate Evidence).
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
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