Several genes are shown to relate to Peters anomaly in humans: PAX6, FOXC1, PITX2, and CYP1B1. These genes are also associated with other disorders .
A PAX6 mutation is found widely in anterior segment malformations, including Peters anomaly. A copy of PAX6 was found to be deleted in a child with Peters anomaly. Also, a copy of the PAX6 gene in a family with dominantly inherited anterior segment malformation was found to have a different amino acid at position 26 .
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Human FOXC1 is on chromosome 6p25 and encodes a 212 amino acid transcription factor, which is characterized by a distinct DNA-binding forkhead domain. Its specific function is unknown, but it is shown to regulate embryonic and ocular development .
The F112S mutation (the amino acid at position 112 is changed from phenylalanine to serine) in FOXC1 gene can cause Axenfeld syndrome and Peters anomaly .
Human PITX2 is on chromosome 4q25 and encodes isoforms by alternative splicing. This transcription factor is involved in the development of the eye, teeth and abdominal organs, and also regulates activities of prolactin in different conditions. Mutations in this gene are also associated with Axenfeld-Rieger syndrome.
A mutation in the third intron of PITX2 is associated with unilateral Peters anomaly. A child carrying the mutation also showed dimorphic features, problems in dental development, and failure of involution of the umbilical skin .
Human CYP1B1 is on chromosome 2p22.2 and encodes an enzyme of 543 amino acids, which localizes to the endoplamic reticulum and is involved in drug metabolism and the synthesis of cholesterol, steroids and other lipids. Since the mutation of this gene is related to primary congenital glaucoma, it is thought that the enzyme also metabolizes a signaling molecule in eye development .
A patient who with Peters anomaly and secondary congenital glaucoma was found to have two novel mutations in CYP1B1; the patient did not have any other malformation or a significant family history. One mutation occurred at position 1 (a change from methionine to threonine), possibly disrupting translation initiation. The other mutation occurred at position 57 and led to a truncated protein .
1. Hanson et al. 1994. Mutations at the Pax6 locus are found in heterogeneous anterior segment malformations including Peter’s anomaly. Nat Genet. Feb;6(2):168-73.NCBI Gene 2. http://www.ncbi.nlm.nih.gov/gene
3. Honkanen et al. 2003. A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene. Am J Ophthalmol. Mar;135(3):368-75.
4. Doward et al. 1999. A mutation in the RIEG1 gene associated with Peters’ anomaly. J Med Genet. Feb;36(2):152-5.
5. Vincent et al. 2001. Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters’ anomaly. J Med Genet. May;38(5):324-6.
6. Vincent et al. 2006. Further support of the role of CYP1B1 in patients with Peters anomaly. Mol Vis. May 16;12:506-10.