Childhood onset hereditary spastic paraplegia

Gene: DSTYK

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

• 28157540

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.

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