TY - JOUR
T1 - Congenital aural atresia associated with agenesis of internal carotid artery in a girl with a FOXI3 deletion
AU - Tassano, Elisa
AU - Jagannathan, Vidhya
AU - Drögemüller, Cord
AU - Leoni, Massimiliano
AU - Hytönen, Marjo K.
AU - Severino, Mariasavina
AU - Gimelli, Stefania
AU - Cuoco, Cristina
AU - Di Rocco, Maja
AU - Sanio, Kirsi
AU - Groves, Andrew K.
AU - Leeb, Tosso
AU - Gimelli, Giorgio
PY - 2015/3/1
Y1 - 2015/3/1
N2 - We report on the molecular characterization of a microdeletion of approximately 2.5Mb 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.
AB - We report on the molecular characterization of a microdeletion of approximately 2.5Mb 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.
KW - Agenesis of internal carotid artery
KW - Array-CGH
KW - Congenital aural atresia
KW - Deletion
KW - FOXI3
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U2 - 10.1002/ajmg.a.36895
DO - 10.1002/ajmg.a.36895
M3 - Article
AN - SCOPUS:84923096219
VL - 167
SP - 537
EP - 544
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 3
ER -