VAX1mutation associated with microphthalmia, corpus callosum agenesis, and orofacial clefting: The first description of aVAX1phenotype in humans
| Autor: | Slavotinek, A.M., Chao, R., Vacik, T., Yahyavi, M., Abouzeid, H., Bardakjian, T., Schneider, A., Shaw, G., Sherr, E.H., Lemke, G., Youssef, M., Schorderet, D.F. |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Proband congenital hereditary and neonatal diseases and abnormalities Cleft Lip Biology Microphthalmia Article Gene Frequency Genetics medicine Humans Microphthalmos Genetics (clinical) Homeodomain Proteins Coloboma Anophthalmia Corpus Callosum Agenesis Homozygote Exons medicine.disease Phenotype eye diseases Cleft Palate HEK293 Cells Amino Acid Substitution Child Preschool Mutation Mutation (genetic algorithm) sense organs PAX6 Agenesis of Corpus Callosum Transcription Factors |
| Zdroj: | Human Mutation, vol. 33, no. 2, pp. 364-368 |
| ISSN: | 1059-7794 |
| Popis: | Vax1 and Vax2 have been implicated in eye development and the closure of the choroid fissure in mice and zebrafish. We sequenced the coding exons of VAX1 and VAX2 in 70 patients with anophthalmia/microphthalmia (A/M). In VAX1, we observed homozygosity for two successive nucleotide substitutions c.453G>A and c.454C>A, predicting p.Arg152Ser, in a proband of Egyptian origin with microphthalmia, small optic nerves, cleft lip/palate, and corpus callosum agenesis. This mutation affects an invariant residue in the homeodomain of VAX1 and was absent from 96 Egyptian controls. It is likely that the mutation results in a loss of function, as the mutation results in a phenotype similar to the Vax1 homozygous null mouse. We did not identify any mutations in VAX2. This is the first description of a phenotype associated with a VAX1 mutation in humans and establishes VAX1 as a new causative gene for A/M. Hum Mutat 33:364-368, 2012. (C) 2011 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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