Deafness and congenital structural abnormalities
Gene: FOXI3
Comment on list classification: Promoting from Red to Green as a recent study (highlighted by GEL Clinical Team) provides corroborating evidence linking FOXI3 with microtia with or without atresia. Sufficient unrelated cases and supported by concordant animal models.Created: 14 Nov 2022, 5:09 p.m. | Last Modified: 14 Nov 2022, 5:09 p.m.
Panel Version: 1.22
Quiat et al. 2022 (PMID: 36260083) reported 4 unrelated families affected by microtia with or without atresia and different predicted deleterious heterozygous variants in the FOXI3 gene. Variants segregated with disease, including in multiplex families, albeit with reduced penetrance. In vitro studies showed that patient variants conferred abnormal FOXI3 nuclear and cytoplasmic localization.
Tassano et al. 2015 (PMID: 25655429) also identified a patient with microtia, aural atresia, and ipsilateral agenesis of the carotid artery who harboured a 2.5 Mb deletion overlapping the FOXI3 gene.
Congenital ear malformations with variable penetrance have been described in a Foxi3 knockout mouse model and haploinsufficient canine breeds supporting a role of FOXI3 in the human phenotype (PMID: 18787161; 24650709)Created: 14 Nov 2022, 5:06 p.m. | Last Modified: 14 Nov 2022, 5:06 p.m.
Panel Version: 1.19
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Microtia with or without atresia
Publications
Not enough clinical evidence at this stageCreated: 17 Oct 2016, 12:39 p.m.
Mode of inheritance
Unknown
Mode of pathogenicity
Other
Comment when marking as ready: Not associated with phenotype in OMIM nor G2P / DD. One 2.5Mb interstitial deletion of the short arm of chromosome 2 at band 2p11.2 found in child with congenital aural atresia associated with agenesis of iInternal carotid artery.Created: 14 Sep 2016, 2:23 p.m.
Phenotypes
Congenital aural atresia
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Red on the Bilateral Microtia Version 1.10 panel.Created: 12 Sep 2016, 2:57 p.m.
FOXI3 is not associated with a phenotype entry in OMIM.Created: 9 Feb 2016, 5:16 p.m.
Publications
Single report. Compelling animal and functional evidence only.Created: 3 Feb 2016, 5:03 p.m.
Publications
Gene: foxi3 has been classified as Green List (High Evidence).
Publications for gene: FOXI3 were set to
Mode of inheritance for gene: FOXI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
26th Oct 2016: the panels Bilateral microtia version 1.10, Ear malformations with hearing impairment version 0.105, and familial hemifacial microsomia version 0.149 gene panels were combined to create this panel. The panel was revised due to expert review, further curation of evidence and internal clinical evaluation. Ready for promotion to version 1.
FOXI3 was added to Deafness and congenital structural abnormalitiespanel. Source: Literature Model of inheritance for gene FOXI3 was set to Unknown
FOXI3 was created by sleigh
FOXI3 was added to Deafness and congenital structural abnormalitiespanel. Sources: Expert list,Expert Review Red