title: Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia.
abstract: Anophthalmia and microphthalmia (AM) are the most severe malformations of the eye, corresponding respectively to reduced size or absent ocular globe. Wide genetic heterogeneity has been reported and different genes have been demonstrated to be causative of syndromic and non-syndromic forms of AM. We screened seven AM genes [GDF6 (growth differentiation factor 6), FOXE3 (forkhead box E3), OTX2 (orthodenticle protein homolog 2), PAX6 (paired box 6), RAX (retina and anterior neural fold homeobox), SOX2 (SRY sex determining region Y-box 2), and VSX2 (visual system homeobox 2 gene)] in a cohort of 150 patients with isolated or syndromic AM. The causative genetic defect was identified in 21% of the patients (32/150). Point mutations were identified by direct sequencing of these genes in 25 patients (13 in SOX2, 4 in RAX, 3 in OTX2, 2 in FOXE3, 1 in VSX2, 1 in PAX6, and 1 in GDF6). In addition eight gene deletions (five SOX2, two OTX2 and one RAX) were identified using a semi-quantitative multiplex polymerase chain reaction (PCR) [quantitative multiplex PCR amplification of short fluorescent fragments (QMPSF)]. The causative genetic defect was identified in 21% of the patients. This result contributes to our knowledge of the molecular basis of AM, and will facilitate accurate genetic counselling.
authors.affiliation: Service de Génétique Médicale, Hôpital Purpan, CHU Toulouse, Toulouse, France; Université Paul-Sabatier Toulouse III, Toulouse, France.
authors.forename: N
authors.initials: N
authors.lastname: Chassaing
authors.forename: A
authors.initials: A
authors.lastname: Causse
authors.forename: A
authors.initials: A
authors.lastname: Vigouroux
authors.forename: A
authors.initials: A
authors.lastname: Delahaye
authors.forename: J-L
authors.initials: JL
authors.lastname: Alessandri
authors.forename: O
authors.initials: O
authors.lastname: Boespflug-Tanguy
authors.forename: O
authors.initials: O
authors.lastname: Boute-Benejean
authors.forename: H
authors.initials: H
authors.lastname: Dollfus
authors.forename: B
authors.initials: B
authors.lastname: Duban-Bedu
authors.forename: B
authors.initials: B
authors.lastname: Gilbert-Dussardier
authors.forename: F
authors.initials: F
authors.lastname: Giuliano
authors.forename: M
authors.initials: M
authors.lastname: Gonzales
authors.forename: M
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: B
authors.initials: B
authors.lastname: Isidor
authors.forename: M-L
authors.initials: ML
authors.lastname: Jacquemont
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.forename: D
authors.initials: D
authors.lastname: Martin-Coignard
authors.forename: M
authors.initials: M
authors.lastname: Mathieu-Dramard
authors.forename: S
authors.initials: S
authors.lastname: Odent
authors.forename: O
authors.initials: O
authors.lastname: Picone
authors.forename: L
authors.initials: L
authors.lastname: Pinson
authors.forename: C
authors.initials: C
authors.lastname: Quelin
authors.forename: S
authors.initials: S
authors.lastname: Sigaudy
authors.forename: A
authors.initials: A
authors.lastname: Toutain
authors.forename: C
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Patrick
authors.initials: P
authors.lastname: Calvas
mesh_terms: D000293:Adolescent; D000328:Adult; D000853:Anophthalmos / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D018740:Genetic Heterogeneity; D055431:Growth Differentiation Factor 6 / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008850:Microphthalmos / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D051857:Otx Transcription Factors / Q000235:genetics; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D017354:Point Mutation / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D005136:Eye Proteins; C404285:FOXE3 protein, human; D051858:Forkhead Transcription Factors; C525906:GDF6 protein, human; D055431:Growth Differentiation Factor 6; 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; D014157:Transcription Factors; C490289:VSX2 protein, human
keywords: FOXE3; GDF6; OTX2; PAX6; RAX; SOX2; VSX2; anophthalmia; microphthalmia