Deafness and congenital structural abnormalities

Gene: FOXI3

Green List (high evidence)

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

• 36260083
• 25655429
• 18787161
• 24650709

I don't know

Not enough clinical evidence at this stage

Created: 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.

I don't know

Phenotypes
Congenital aural atresia

Publications

• 25655429

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.

Red List (low evidence)

FOXI3 is not associated with a phenotype entry in OMIM.

Created: 9 Feb 2016, 5:16 p.m.

Publications

• PMID:18787161

Red List (low evidence)

Single report. Compelling animal and functional evidence only.

Created: 3 Feb 2016, 5:03 p.m.

Publications

• 25655429