title: Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma.
abstract: Severe ocular malformations, including anophthalmia-microphthalmia (AM), are responsible for around 25% of severe visual impairment in childhood. Recurrent interstitial deletions of 14q22-23 are associated with AM and a wide range of extra-ocular phenotypes including brain anomalies. The homeobox gene OTX2 is located at 14q22.3 and has recently been identified as mutated in AM patients. Eight human OTX2 mutations have been reported in subjects with severe eye malformations, including AM, and variable developmental delay. We screened a novel AM cohort for mutations and deletions in OTX2, and identified four new mutations in six individuals and two cases of whole gene deletions. Our data suggest that OTX2 mutations and deletions account for 2-3% of AM cases.
authors.affiliation: Dept of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wyatt
authors.forename: Preeti
authors.initials: P
authors.lastname: Bakrania
authors.forename: David J
authors.initials: DJ
authors.lastname: Bunyan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Osborne
authors.forename: John A
authors.initials: JA
authors.lastname: Crolla
authors.forename: Alison
authors.initials: A
authors.lastname: Salt
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Ruth
authors.initials: R
authors.lastname: Newbury-Ecob
authors.forename: Y
authors.initials: Y
authors.lastname: Abou-Rayyah
authors.forename: J Richard O
authors.initials: JR
authors.lastname: Collin
authors.forename: David
authors.initials: D
authors.lastname: Robinson
authors.forename: Nicola
authors.initials: N
authors.lastname: Ragge
mesh_terms: D000293:Adolescent; D000853:Anophthalmos / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14; D003103:Coloboma / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008850:Microphthalmos / Q000235:genetics*; D051857:Otx Transcription Factors / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: C497659:OTX2 protein, human; D051857:Otx Transcription Factors