title: SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia.
abstract: Anophthalmia (A) and microphthalmia (M) are rare developmental anomalies that have significant effects on visual activity. In fraction of A/M subjects, single genetic defects have been identified as causative. In this study we analysed 65 Italian A/M patients, 21 of whom are syndromic, for mutations in SOX2, OTX2 and PAX6 genes. In syndromic patients the presence of genome imbalances through array CGH was also investigated. No mutations were found for OTX2 and PAX6 genes. Three causative SOX2 mutations were found in subjects with syndromic A. In a subject with syndromic signs and monolateral M, two de novo 6.26 Mb and 1.37 Mb deletions in 4q13.2q13.3 have been identified. A SOX2 missense (p.Ala161Ser) mutation was found in 1 out of 39 a subject with non-syndromic monolateral M. Alanine at position 161 is conserved along phylogeny and the p.Ala161Ser mutation is estimated pathogenic by in silico analysis. However, this mutation was also present in the unaffected patient's daughter.
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mauri
authors.affiliation: Institute of Genetics, Azienda Ospedaliero-Universitaria Udine, Udine, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Franzoni
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Scarcello
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sala
authors.affiliation: Clinical Genetics Unit, IRCCS Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Garavelli
authors.affiliation: Ophthalmologist, Roma, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Modugno
authors.affiliation: Department of Molecular Medicine, "La Sapienza" University, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Patrosso
authors.affiliation: Pediatric Ophthalmology, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Piozzi
authors.affiliation: Pediatric Ophthalmology, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Del Longo
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Giovanni P
authors.initials: GP
authors.lastname: Gesu
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Manfredini
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Primignani
authors.affiliation: Institute of Genetics, Azienda Ospedaliero-Universitaria Udine, Udine, Italy; Department of Medical and Biological Sciences, Udine University, Udine, Italy. Electronic address: giuseppe.damante@uniud.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy. Electronic address: silvana.penco@ospedaleniguarda.it.
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000853:Anophthalmos / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007558:Italy; D008297:Male; D008850:Microphthalmos / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D051857:Otx Transcription Factors / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: Anophthalmia; Microphthalmia; OTX2; PAX6; SOX2