title: Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia.
abstract: Ocular (uveoretinal) colobomas occur in one in 10,000 individuals and present a substantive cause of congenital poor vision. The genetic bases of most forms of uveoretinal coloboma are elusive; mutations in PAX2 are found in only a few cases of coloboma of the retina and optic nerve that occur with renal anomalies as part of the renal-coloboma syndrome (MIM#120330; #167409). From experimental data that upstream expression of sonic hedgehog (SHH) controls Pax2 expression in mice and zebrafish, and from clinical experience that colobomas are observed frequently in patients with holoprosencephaly, we hypothesized that SHH could be a candidate for non-syndromic ocular colobomas (NSOC). We identified a three-generation family in which both a proband and his mother presented with iris and uveoretinal colobomas without optic nerve involvement. A novel 24 bp deletion in the gene SHH was identified in these affected family members, and cosegregated with the phenotype. This is the first report of the association of SHH mutations and uveoretinal coloboma.
authors.affiliation: UCLA Department of Human Genetics, Pediatrics, The Jules Stein Eye Institute and Mental Retardation Research Center, Los Angeles, California, USA. las@umn.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Schimmenti
authors.forename: June
authors.initials: J
authors.lastname: de la Cruz
authors.forename: Richard Alan
authors.initials: RA
authors.lastname: Lewis
authors.forename: J D
authors.initials: JD
authors.lastname: Karkera
authors.forename: Glenda S
authors.initials: GS
authors.lastname: Manligas
authors.forename: Erich
authors.initials: E
authors.lastname: Roessler
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
mesh_terms: D000328:Adult; D001483:Base Sequence; D003103:Coloboma / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D005192:Family Health; D005260:Female; D053823:Hedgehog Proteins; D006801:Humans; D007223:Infant; D008297:Male; D008850:Microphthalmos / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D017384:Sequence Deletion; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D053823:Hedgehog Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D004247:DNA