title: Ocular and craniofacial phenotypes in a large Brazilian family with congenital aniridia.
abstract: Congenital aniridia is a rare genetic disorder characterized by varying degrees of iris hypoplasia that are associated with additional ocular abnormalities. More than 90% of the causal mutations identified are found in the PAX6 gene, a transcription factor of critical importance in the process of neurogenesis and ocular development. Here, we investigate clinical, molecular, and craniofacial features of a large Brazilian family with congenital aniridia. Among the 56 eyes evaluated, phenotype variation encompassed bilateral total aniridia to mild iris defects with extensive variation between eyes of the same individual. PAX6 molecular screening indicated a heterozygous splice mutation (c.141 + 1G>A). Thus, we hypothesize that this splicing event may cause variation in the expression of the wild-type transcript, which may lead to the observed variation in phenotype. Affected individuals were more brachycephalic, even though their face height and cephalic circumference were not significantly different when compared to those of non-affected relatives. From this, we infer that the head shape of affected subjects may also be a result of the PAX6 splice-site mutation. Our data summarize the clinical variability associated with the ocular phenotype in a large family with aniridia, and help shed light on the role of PAX6 in neurocranial development.
authors.affiliation: Programa de Pós-Graduação em Genética e Biologia Molecular, Departamento de Genética, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; gINAGEMP - Instituto Nacional de Genética Médica Populacional, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Fernandes-Lima
authors.forename: V R
authors.initials: VR
authors.lastname: Paixão-Côrtes
authors.forename: A K M de
authors.initials: AK
authors.lastname: Andrade
authors.forename: A S
authors.initials: AS
authors.lastname: Fernandes
authors.forename: B N L
authors.initials: BN
authors.lastname: Coronado
authors.forename: H P
authors.initials: HP
authors.lastname: Monte Filho
authors.forename: M J
authors.initials: MJ
authors.lastname: Santos
authors.forename: R L de
authors.initials: RL
authors.lastname: Omena Filho
authors.forename: F C
authors.initials: FC
authors.lastname: Biondi
authors.forename: A
authors.initials: A
authors.lastname: Ruiz-Linares
authors.forename: V
authors.initials: V
authors.lastname: Ramallo
authors.forename: T
authors.initials: T
authors.lastname: Hünemeier
authors.forename: L
authors.initials: L
authors.lastname: Schuler-Faccini
authors.forename: I L
authors.initials: IL
authors.lastname: Monlleó
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015783:Aniridia / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D001938:Brazil; D002648:Child; D019465:Craniofacial Abnormalities / Q000473:pathology*; D005124:Eye Abnormalities / Q000473:pathology*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins
keywords: PAX6; aniridia; autosomal dominant; neurocranium