title: SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies.
abstract: The SOX2 transcription factor is expressed early in the embryonic stem cells of the blastocyst and later in the neural stem cells. It is a member of the SOX family of proteins that carry a DNA-binding high-mobility group domain and additional domains that regulate embryonic development and cell fate determinations. We surveyed 93 patients with severe eye malformations for mutations in SOX2. Here, we report a novel nonsense mutation in one female patient with bilateral clinical anophthalmia, absence of all optic pathways, and other neurological abnormalities. The mutation, Q155X, creates a premature termination codon early in the transcriptional activation domain and is likely to be a null allele. Our data show that mutations in SOX2 can cause not only anophthalmia, but also aplasia of the optic nerve, chiasm and optic tract, as well as modest bilateral sensorineural hearing loss, and global developmental delay, underscoring the importance of SOX2 in early human eye and brain development.
authors.affiliation: Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. hagstrs@ccf.org
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Hagstrom
authors.forename: Gayle J T
authors.initials: GJ
authors.lastname: Pauer
authors.forename: Janet
authors.initials: J
authors.lastname: Reid
authors.forename: Ellen
authors.initials: E
authors.lastname: Simpson
authors.forename: Sue
authors.initials: S
authors.lastname: Crowe
authors.forename: Irene H
authors.initials: IH
authors.lastname: Maumenee
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000853:Anophthalmos / Q000473:pathology*; D001483:Base Sequence; D001921:Brain / Q000002:abnormalities*; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D024002:HMGB Proteins / Q000235:genetics*; D034381:Hearing Loss / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D024002:HMGB Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors