title: Congenital aural atresia associated with agenesis of internal carotid artery in a girl with a FOXI3 deletion.
abstract: We report on the molecular characterization of a microdeletion of approximately 2.5 Mb at 2p11.2 in a female baby with left congenital aural atresia, microtia, and ipsilateral internal carotid artery agenesis. The deletion was characterized by fluorescence in situ hybridization, array comparative genomic hybridization, and whole genome re-sequencing. Among the genes present in the deleted region, we focused our attention on the FOXI3 gene. Foxi3 is a member of the Foxi class of Forkhead transcription factors. In mouse, chicken and zebrafish Foxi3 homologues are expressed in the ectoderm and endoderm giving rise to elements of the jaw as well as external, middle and inner ear. Homozygous Foxi3-/- mice have recently been generated and show a complete absence of the inner, middle, and external ears as well as severe defects in the jaw and palate. Recently, a 7-bp duplication within exon 1 of FOXI3 that produces a frameshift and a premature stop codon was found in hairless dogs. Mild malformations of the outer auditory canal (closed ear canal) and ear lobe have also been noted in a fraction of FOXI3 heterozygote Peruvian hairless dogs. Based on the phenotypes of Foxi3 mutant animals, we propose that FOXI3 may be responsible for the phenotypic features of our patient. Further characterization of the genomic region and the analysis of similar patients may help to demonstrate this point.
authors: Istituto Giannina Gaslini, Genova, Italy.
authors: Elisa
authors: E
authors: Tassano
authors: Vidhya
authors: V
authors: Jagannathan
authors: Cord
authors: C
authors: Drögemüller
authors: Massimiliano
authors: M
authors: Leoni
authors: Marjo K
authors: MK
authors: Hytönen
authors: Mariasavina
authors: M
authors: Severino
authors: Stefania
authors: S
authors: Gimelli
authors: Cristina
authors: C
authors: Cuoco
authors: Maja
authors: M
authors: Di Rocco
authors: Kirsi
authors: K
authors: Sanio
authors: Andrew K
authors: AK
authors: Groves
authors: Tosso
authors: T
authors: Leeb
authors: Giorgio
authors: G
authors: Gimelli
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000792:Angiography; D000818:Animals; D002343:Carotid Artery, Internal / Q000002:abnormalities*; D002871:Chromosome Banding; D055028:Comparative Genomic Hybridization; D000013:Congenital Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D004285:Dogs; D004423:Ear / Q000002:abnormalities*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D017353:Gene Deletion; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D023281:Genomics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D010641:Phenotype; D014057:Tomography, X-Ray Computed
chemical_list: D051858:Forkhead Transcription Factors; C000602636:Foxi3 protein, human
keywords: FOXI3; agenesis of internal carotid artery; array-CGH; congenital aural atresia; deletion
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