title: Mutation in the human homeobox gene NKX5-3 causes an oculo-auricular syndrome.
abstract: Several dysmorphic syndromes affect the development of both the eye and the ear, but only a few are restricted to the eye and the external ear. We describe a developmental defect affecting the eye and the external ear in three members of a consanguineous family. This syndrome is characterized by ophthalmic anomalies (microcornea, microphthalmia, anterior-segment dysgenesis, cataract, coloboma of various parts of the eye, abnormalities of the retinal pigment epithelium, and rod-cone dystrophy) and a particular cleft ear lobule. Linkage analysis and mutation screening revealed in the first exon of the NKX5-3 gene a homozygous 26 nucleotide deletion, generating a truncating protein that lacked the complete homeodomain. Morpholino knockdown expression of the zebrafish nkx5-3 induced microphthalmia and disorganization of the developing retina, thus confirming that this gene represents an additional member implicated in axial patterning of the retina.
authors.affiliation: Institut de Recherche en Ophtalmologie, 1950 Sion, Switzerland. daniel.schorderet@irovision.ch
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: Olivia
authors.initials: O
authors.lastname: Nichini
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Boisset
authors.forename: Bozena
authors.initials: B
authors.lastname: Polok
authors.forename: Leila
authors.initials: L
authors.lastname: Tiab
authors.forename: Hélène
authors.initials: H
authors.lastname: Mayeur
authors.forename: Bahija
authors.initials: B
authors.lastname: Raji
authors.forename: Gauillaume
authors.initials: G
authors.lastname: de la Houssaye
authors.forename: Marc M
authors.initials: MM
authors.lastname: Abitbol
authors.forename: Francis L
authors.initials: FL
authors.lastname: Munier
mesh_terms: D000368:Aged; D000818:Animals; D003241:Consanguinity; D004423:Ear / Q000002:abnormalities*; D004622:Embryo, Mammalian / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005124:Eye Abnormalities / Q000196:embryology / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010375:Pedigree; D013577:Syndrome; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism
chemical_list: C530064:HMX1 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors