Hereditary spastic paraplegia - childhood onset

Gene: DSTYK

Amber List (moderate evidence)

DSTYK (dual serine/threonine and tyrosine protein kinase)
EnsemblGeneIds (GRCh38): ENSG00000133059
EnsemblGeneIds (GRCh37): ENSG00000133059
OMIM: 612666, Gene2Phenotype
DSTYK is in 12 panels

3 reviews

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

I don't know

Childhood onset. Three families with same founder mutation.
Created: 9 May 2019, 12:10 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Louise Daugherty (Genomics England Curator)

I don't know

Red gene with Green and Amber 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.
Red rating on Hereditary spastic paraplegia panel 1.198

Added 'Founder effect' tag based on haplotype analysis in Lee et al. (2017, PMID:28157540) which indicates a founder effect- the same deletion/insertion was identified in 3 unrelated families. At the time of curation, PMID:28157540 provides all evidence for the disease:gene association.
Rebecca Foulger (Genomics England curator), 11 May 2017

In affected members of 3 unrelated families of Middle Eastern descent with spastic paraplegia-23 (MIM:270750) Lee et al. (2017, PMID:28157540) identified a homozygous intragenic deletion/insertion in the DSTYK gene. The deletion segregated with the disorder in all 3 families. Haplotype analysis indicated a founder effect. The deletion insertion consisted of a 4-kb deletion associated with a 20-bp insertion, resulting in the removal of the last 2 exons of DSTYK (exons 12 and 13) along with part of the 3-prime untranslated region.
Rebecca Foulger (Genomics England curator), 11 May 2017
Created: 2 May 2019, 3:54 p.m.

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

Green List (high evidence)

associated with pigmentary abnormalities, including premature graying of the hair and vitiligo-like or hyperpigmented skin lesions. Some patients may also have a peripheral neuropathy. 3 unrelated families of Middle Eastern descent with spastic paraplegia-23 . 7 affected members of a Sardinian family (K100) with congenital anomalies of the kidney and urinary tract-1-incomplete penetrance
Created: 28 Apr 2019, 4:16 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Congenital anomalies of kidney and urinary tract 1, 610805, AD; Spastic paraplegia 23, 270750, AR

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Yorkshire and North East GLH
  • NHS GMS
  • London North GLH
  • Other
Phenotypes
  • Spastic paraplegia 23, 270750
  • ongenital anomalies of kidney and urinary tract 1, 610805, AD
  • Spastic paraplegia 23, 270750, AR
OMIM
612666
Clinvar variants
Variants in DSTYK
Penetrance
None
Publications
Panels with this gene

History Filter Activity

21 May 2019, Gel status: 2

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Amber was added to DSTYK. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)

13 May 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to DSTYK.

2 May 2019, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

28 Apr 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

28 Apr 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: DSTYK were changed from Spastic paraplegia 23, 270750 to Spastic paraplegia 23, 270750; ongenital anomalies of kidney and urinary tract 1, 610805, AD; Spastic paraplegia 23, 270750, AR

28 Apr 2019, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: DSTYK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

28 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to DSTYK.

28 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to DSTYK.

3 Apr 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes Spastic paraplegia 23, 270750 for gene: DSTYK

28 Jan 2019, Gel status: 1

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Rebecca Foulger: Comment on list classification

19 Dec 2018, Gel status: 1

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

Sarah Leigh (Genomics England Curator)

gene: DSTYK was added gene: DSTYK was added to Hereditary spastic paraplegia - childhood onset. Sources: Other Mode of inheritance for gene: DSTYK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DSTYK were set to 28157540 Phenotypes for gene: DSTYK were set to Spastic paraplegia 23, 270750