title: Asymmetric phenotype of Axenfeld-Rieger anomaly and aniridia associated with a novel PITX2 mutation.
abstract: OBJECTIVE
  To evaluate the asymmetry of the anterior segment phenotype between the two eyes of a patient with Axenfeld-Rieger syndrome (ARS).
  
  
  METHODS
  The entire database of a tertiary glaucoma practice was screened for patients with ARS. The medical records of patients with ARS were reviewed. The clinical characteristics of ocular examination of the two eyes of each patient were recorded and compared. Dental and medical information were also reviewed where available. The anterior segment phenotype was tabulated to assess asymmetry. Asymmetric anterior segment characteristics of patients with ARS were compared with reported cases in the literature.
  
  
  RESULTS
  Eight patients with ARS were identified from screening of more than 5,000 patients of a tertiary glaucoma practice. All patients had Axenfeld-Rieger anomaly in both eyes except one patient presented with an asymmetric phenotype of the anterior segment with features of Axenfeld-Rieger anomaly in one eye, but aniridia in the other eye. This patient had non-ocular findings including flat midface, hypodontia with lack of an upper incisor, and redundant periumbilical skin, typical for ARS. A heterozygous C>T nucleotide substitution was identified in exon 4 of the pituitary homeobox 2 (PITX2) gene, resulting in the replacement of a glutamine codon (CAG) with a stop codon (TAG) at amino acid position 67. This mutation is denoted c.199C>T at the cDNA level or p.Gln67Stop (or Q67X) at the protein level. Only three cases with asymmetric anterior segment phenotype between the two eyes of a patient with AGS have been reported in the literature.
  
  
  CONCLUSIONS
  Variability in phenotype may occur between the two eyes of an individual affected by ARS. The current case undermines the advantage of genetic testing to correctly diagnose a rare disease.
authors: Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. law@jsei.ucla.edu
authors: Simon K
authors: SK
authors: Law
authors: Maha
authors: M
authors: Sami
authors: Natik
authors: N
authors: Piri
authors: Anne L
authors: AL
authors: Coleman
authors: Joseph
authors: J
authors: Caprioli
references: Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2456-60
references: 10937553
references: Am J Ophthalmol. 1998 Jan;125(1):98-100
references: 9437321
references: Cell Mol Life Sci. 2000 Oct;57(11):1652-66
references: 11092457
references: Expert Rev Mol Med. 2005 Nov 08;7(25):1-17
references: 16274491
references: Arch Ophthalmol. 1979 Nov;97(11):2120-2
references: 508179
references: Acta Ophthalmol Scand. 2001 Apr;79(2):201-3
references: 11284764
references: Hum Mol Genet. 2000 Sep 1;9(14):2131-9
references: 10958652
references: Am J Ophthalmol. 2000 Jul;130(1):107-15
references: 11004268
references: Am J Pathol. 2004 Nov;165(5):1633-41
references: 15509533
references: Hum Mol Genet. 2002 May 15;11(10):1177-84
references: 12015277
references: Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3573-9
references: 19279310
references: Arch Ophthalmol. 1965 Jun;73:810-7
references: 14302514
references: Trans Am Ophthalmol Soc. 1983;81:736-84
references: 6676983
references: Hum Mol Genet. 2001 Aug 1;10(16):1631-8
references: 11487566
references: Eur J Hum Genet. 2009 Dec;17(12):1527-39
references: 19513095
references: Hum Mutat. 1998;11(2):93-108
references: 9482572
references: Hum Mol Genet. 2006 Mar 15;15(6):905-19
references: 16449236
references: Trends Genet. 1999 Feb;15(2):74-80
references: 10098411
references: Pediatr Res. 2003 Dec;54(6):791-6
references: 14561779