Childhood onset hereditary spastic paraplegia
Gene: DSTYK
Childhood onset. Three families with same founder mutation.Created: 9 May 2019, 12:10 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
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 2017Created: 2 May 2019, 3:54 p.m.
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 penetranceCreated: 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
Source Expert Review Amber was added to DSTYK. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Source Yorkshire and North East GLH was added to DSTYK.
Gene: dstyk has been classified as Red List (Low Evidence).
Gene: dstyk has been classified as Green List (High Evidence).
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
Mode of inheritance for gene: DSTYK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Source NHS GMS was added to DSTYK.
Source London North GLH was added to DSTYK.
Added phenotypes Spastic paraplegia 23, 270750 for gene: DSTYK
Rebecca Foulger: Comment on list classification
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