title: VSX2 mutations in autosomal recessive microphthalmia.
abstract: OBJECTIVE
  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.
authors: Department of Pediatrics and Children’s Research Institute at the Medical College of Wisconsin, Children’s Hospital of Wisconsin, Milwaukee, WI, USA.
authors: Linda M
authors: LM
authors: Reis
authors: Ayesha
authors: A
authors: Khan
authors: Ariana
authors: A
authors: Kariminejad
authors: Farhad
authors: F
authors: Ebadi
authors: Rebecca C
authors: RC
authors: Tyler
authors: Elena V
authors: EV
authors: Semina
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000853:Anophthalmos / Q000150:complications / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D003241:Consanguinity; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008850:Microphthalmos / Q000150:complications / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics*; D015027:Zebrafish
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C490289:VSX2 protein, human