VSX2 mutations in autosomal recessive microphthalmia. Mol Vis 2011;17:2527-32
Date
10/07/2011Pubmed ID
21976963Pubmed Central ID
PMC3185030Scopus ID
2-s2.0-83055174002 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
PURPOSE: To further explore the spectrum of mutations in the Visual System Homeobox 2 (VSX2/CHX10) gene previously found to be associated with autosomal recessive microphthalmia.
METHODS: We screened 95 probands with syndromic or isolated developmental ocular conditions (including 55 with anophthalmia/microphthalmia) for mutations in VSX2.
RESULTS: Homozygous mutations in VSX2 were identified in two out of five consanguineous families with isolated microphthalmia. A novel missense mutation, c.668G>C (p.G223A), was identified in a large Pakistani family with multiple sibships affected with bilateral microphthalmia. This p.G223A mutation affects the conserved CVC motif that was shown to be important for DNA binding and repression activities of VSX2. The second mutation, c.249delG (p.Leu84SerfsX57), was identified in an Iranian family with microphthalmia; this mutation has been previously reported and is predicted to generate a severely truncated mutant protein completely lacking the VSX2 homeodomain, CVC domain and COOH-terminal regions.
CONCLUSIONS: Mutations in VSX2 represent an important cause of autosomal recessive microphthalmia in consanguineous pedigrees. Identification of a second missense mutation in the CVC motif emphasizes the importance of this region for normal VSX2 function.
Author List
Reis LM, Khan A, Kariminejad A, Ebadi F, Tyler RC, Semina EVAuthor
Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Anophthalmos
Base Sequence
Case-Control Studies
Child
Consanguinity
Conserved Sequence
DNA Mutational Analysis
Female
Genes, Recessive
Homeodomain Proteins
Homozygote
Humans
Male
Mice
Microphthalmos
Molecular Sequence Data
Mutation
Pedigree
Retina
Sequence Alignment
Transcription Factors
Zebrafish
