title: SOX2 anophthalmia syndrome.
abstract: Heterozygous, de novo, loss-of-function mutations in SOX2 have been shown to cause bilateral anophthalmia. Here we provide a detailed description of the clinical features associated with SOX2 mutations in the five individuals with reported mutations and four newly identified cases (including the first reported SOX2 missense mutation). The SOX2-associated ocular malformations are variable in type, but most often bilateral and severe. Of the nine patients, six had bilateral anophthalmia and two had anophthalmia with contralateral microphthalmia with sclerocornea. The remaining case had anophthalmia with contralateral microphthalmia, posterior cortical cataract and a dysplastic optic disc, and was the only patient to have measurable visual acuity. The relatively consistent extraocular phenotype observed includes: learning disability, seizures, brain malformation, specific motor abnormalities, male genital tract malformations, mild facial dysmorphism, and postnatal growth failure. Identifying SOX2 mutations from large cohorts of patients with structural eye defects has delineated a new, clinically-recognizable, multisystem disorder and has provided important insight into the developmental pathways critical for morphogenesis of the eye, brain, and male genital tract.
authors.affiliation: Adnexal Service, Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Ragge
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
authors.forename: Adele
authors.initials: A
authors.lastname: Schneider
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Luisa
authors.initials: L
authors.lastname: de Sanctis
authors.forename: Ugo
authors.initials: U
authors.lastname: de Sanctis
authors.forename: Alison
authors.initials: A
authors.lastname: Salt
authors.forename: J Richard O
authors.initials: JR
authors.lastname: Collin
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Vivian
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Free
authors.forename: Pamela
authors.initials: P
authors.lastname: Thompson
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Williamson
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Sisodiya
authors.forename: Veronica
authors.initials: V
authors.lastname: van Heyningen
authors.forename: David R
authors.initials: DR
authors.lastname: Fitzpatrick
mesh_terms: D000293:Adolescent; D000853:Anophthalmos / Q000235:genetics* / Q000473:pathology; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D024002:HMGB Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D055748:SOXB1 Transcription Factors; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024002:HMGB Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D004247:DNA