Familial cerebral small vessel disease
Gene: FOXC1PMID: 32720677 - Ferre-Fernández et al 2020 - zebrafish knockout lines with combinations of the two orthologs of FOXC1 in zebrafish, foxc1a and foxc1b. 3 phenotypes:
1. foxc1a−/− single knockout homozygous embryos and foxc1−/− double knockout homozygous embryos - severe global vascular defects and early lethality, as well as microphthalmia, periocular edema and absence of the anterior chamber of the eye
2. fish with heterozygous loss of foxc1a combined with homozygosity for foxc1b (foxc1a+/−;foxc1b−/−) demonstrated craniofacial defects, heart anomalies and scoliosis
3. All other single and combined genotypes appeared normal.Created: 6 Oct 2020, 3:56 p.m. | Last Modified: 6 Oct 2020, 3:56 p.m.
Panel Version: 1.9
Publications
Comment when marking as ready: Associated with phenotype in G2P. Numerous variants reported in this phenotype.Created: 4 Jul 2016, 9:28 a.m.
Comment on list classification: Tier 1 gene for Cerebral Small Vessel Disorders in BRIDGE StudyCreated: 4 Jul 2016, 9:19 a.m.
FOXC1-deletion related cerebral small vessel disease is caused by mutations or deletions in the FOXC1 gene (chromosome 6p25). FOXC1 deletions cause Axenfeld-Rieger Syndrome, cerebellar malformations and developmental abnormalities. These patients have also been shown to have white matter hyperintensities on MRI.
In multiple cases of Axenfeld-Rieger Syndrome and other FOXC1-deletion related syndromes, white matter hyperintensities on brain imaging have been reported.
In a genome-wide association analysis, linked SNPs which influence FOXC1 transcript levels and FOXC1 function were also demonstrated to associate with cerebral small vessel disease. Patients with missense and nonsense mutations, as well as duplications and deletions involving the FOXC1 region were also shown to have imaging features of cerebral small vessel disease.Created: 22 Jun 2016, 3:07 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
stroke; Axenfled Rieger Syndrome, Cerebellar malformations; Dandy Walker Syndrome; Hearing Impairment
Publications
Publications for gene: FOXC1 were set to 22678982; 22903608; 25250569; 16551997; 23686687
This gene has been classified as Green List (High Evidence).
Phenotypes for FOXC1 were set to Stroke; Dandy Walker Syndrome; Hearing Impairment; Axenfeld-Rieger syndrome, type 3, Rieger or Axenfeld anomalies 602482; Iridogoniodysgenesis, type 1, Iris hypoplasia and glaucoma 601631
Publications for FOXC1 were set to 22678982; 22903608; 25250569; 16551997; 23686687
FOXC1 was added to Familial cerebral small vessel diseasepanel. Sources: Expert list,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,UKGTN
This gene has been classified as Green List (High Evidence).
FOXC1 was added to Familial cerebral small vessel diseasepanel. Sources: Literature
FOXC1 was created by rheatan