Cerebral vascular malformations

Gene: THSD1

Amber List (moderate evidence)

THSD1 (thrombospondin type 1 domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000136114
EnsemblGeneIds (GRCh37): ENSG00000136114
OMIM: 616821, Gene2Phenotype
THSD1 is in 1 panel

3 reviews

Louise Daugherty (Genomics England Curator)

I don't know

Downgraded from Green to Amber. Combined reviews: Ian Berry (YNELGH) & GEL clinical team (Richard Scott & Helen Brittain) - Amber in view intracerebral aneurysms. Unclear on penetrance.
Created: 3 Dec 2019, 2:02 p.m. | Last Modified: 3 Dec 2019, 2:02 p.m.
Panel Version: 1.70

Alice Gardham (Genomics England)

Comment on list classification: Mutations identified in nine families with intracerebral aneurysms. Good animal models support this result
Created: 15 Dec 2016, 9:45 a.m.

Ellen McDonagh (Genomics England Curator)

Novel associated reported in PMID: 27895300 - segregation of the R450X variant was reported in all affected members of a large family with an logarithm of odds (LOD) score of 4.69 (disease frequency =0.032; penetrance=100%; R450X allele frequency=0.001). The variant was heterozygous in all affected people, obligate carriers, and 3 members with unknown clinical status. The mutation was absent in unaffected relatives, the control cohort (n=305), and 89040 chromosomes in the ExAC database. Variants found in 507 unrelated patients were enriched versus those in ExAC - In 8 unrelated probands, including those with sporadic disease, THSD1 missense mutations were identified that either exist in the signal peptide (L5F in 2 probands) or cluster in the intracellular region (R460W, E466G, G600E, P639L, T653I, and S775P). In a zebrafish model, loss of thsd1 caused intracranial hemorrhages by 48 hours. In a subset of mutant mice, brain magnetic resonance imagings revealed mild to severe dilatation of cerebral ventricles, consistent with hydrocephalus as young as 8 weeks.
Created: 14 Dec 2016, 2:52 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
subarachnoid hemorrhage

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Literature
Phenotypes
  • subarachnoid hemorrhage
OMIM
616821
Clinvar variants
Variants in THSD1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

29 Nov 2019, Gel status: 2

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Amber was added to THSD1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)

29 Nov 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to THSD1.

29 Nov 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to THSD1.

19 Dec 2016, Gel status: 4

panel promoted to version 1

Alice Gardham (Genomics England)

Promoted to version 1 on the 19th December 2016

15 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Green List (High Evidence).

15 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Green List (High Evidence).

14 Dec 2016, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

THSD1 was added to Cerebrovascular disorderspanel. Sources: Literature

14 Dec 2016, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

THSD1 was created by ellenmcdonagh