RESUMO
Anophthalmia or microphthalmia (A/M), characterized by absent or small eye, can be unilateral or bilateral and represent developmental anomalies due to the mutations in several genes. Recently, mutations in aldehyde dehydrogenase family 1, member A3 (ALDH1A3) also known as retinaldehyde dehydrogenase 3, have been reported to cause A/M. Here, we screened a cohort of 75 patients with A/M and showed that mutations in ALDH1A3 occurred in six families. Based on this series, we estimate that mutations in ALDH1A3 represent a major cause of A/M in consanguineous families, and may be responsible for approximately 10% of the cases. Screening of this gene should be performed in a first line of investigation, together with SOX2.
Assuntos
Aldeído Oxirredutases/genética , Anoftalmia/genética , Consanguinidade , Microftalmia/genética , Mutação , Sequência de Aminoácidos , Anoftalmia/enzimologia , Anoftalmia/patologia , Sequência de Bases , Olho/enzimologia , Olho/patologia , Feminino , Genótipo , Humanos , Masculino , Microftalmia/enzimologia , Microftalmia/patologia , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Fenótipo , Alinhamento de SequênciaRESUMO
Waardenburg anophthalmia syndrome, also known as microphthalmia with limb anomalies, ophthalmoacromelic syndrome, and anophthalmia-syndactyly, is a rare autosomal-recessive developmental disorder that has been mapped to 10p11.23. Here we show that this disease is heterogeneous by reporting on a consanguineous family, not linked to the 10p11.23 locus, whose two affected children have a homozygous mutation in SMOC1. Knockdown experiments of the zebrafish smoc1 revealed that smoc1 is important in eye development and that it is expressed in many organs, including brain and somites.