VAX1 Mutation Associated with Microphthalmia, Corpus Callosum Agenesis, and Orofacial Clefting: the First Description of a VAX1 Phenotype in Humans

Overview

Journal Hum Mutat

Specialty Genetics

Date 2011 Nov 19

PMID 22095910

Citations 32

Authors

Anne M Slavotinek

Ryan Chao

Tomas Vacik

Mani Yahyavi

Hana Abouzeid

Tanya Bardakjian

Adele Schneider

Gary Shaw

Elliott H Sherr

Greg Lemke

Mohammed Youssef

Daniel F Schorderet

Affiliations

Soon will be listed here.

Abstract

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.

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