Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic
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, 3:55 p.m. | Last Modified: 6 Oct 2020, 3:55 p.m.
Panel Version: 0.4807
Phenotypes
eye and vascular development
Publications
Comment when marking as ready: Appears to be a distinct association but I agree, the pathogenicity of the variants is not firmly established.Created: 30 Sep 2020, 8:26 a.m. | Last Modified: 30 Sep 2020, 8:26 a.m.
Panel Version: 0.74
Seven FOXC1 'pathogenic' variants in 8 CAKUT families identified through WES. All individuals carrying the FOXC1 pathogenic variants are heterozygote. There was incomplete penetrance and variable expressivity in families. None of the 7 pathogenic variants were reported before in patients with Axenfeld–Rieger syndrome, anterior segment dysgenesis, or congenital glaucoma. Two of the seven pathogenic variants are novel, i.e., they were never observed in the population database before, including the gnomAD database that collects 141,456 control individuals.34 The other five pathogenic variants, though reported in the population database, are present in less than five individuals as a heterozygote. The locations of these pathogenic variants do not cluster in the forkhead domain (where variants causing Axenfeld–Rieger syndrome or anterior segment dysgenesis are located).
NB they call them pathogenic - but no documentation of ACMG criteria used.
Previous animal studies show CAKUT in homozygous and heterozygous mice.Created: 30 Sep 2020, 4:19 a.m. | Last Modified: 30 Sep 2020, 4:19 a.m.
Panel Version: 0.69
CAKUT not a feature of this syndromeCreated: 27 Nov 2019, 11:40 p.m. | Last Modified: 27 Nov 2019, 11:40 p.m.
Panel Version: 0.0
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Congenital anomalies of the kidney and urinary tract (CAKUT)
Publications
Gene: foxc1 has been classified as Amber List (Moderate Evidence).
Gene: foxc1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: FOXC1 were changed from to Congenital anomalies of the kidney and urinary tract (CAKUT)
Publications for gene: FOXC1 were set to 32475988
Publications for gene: FOXC1 were set to
Mode of inheritance for gene: FOXC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: foxc1 has been classified as Amber List (Moderate Evidence).
Gene: foxc1 has been classified as Red List (Low Evidence).
Gene: foxc1 has been classified as Red List (Low Evidence).
gene: FOXC1 was added gene: FOXC1 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: FOXC1 was set to Unknown