Molecular and Clinical Characterization of a Patient with Deletion of Chromosome 12q21-22 and Cornea Plana

Abstract

Abstract: : Purpose: To determine the molecular boundaries of a chromosome 12 deletion in a patient with cornea plana. Methods: A patient with an interstitial deletion of chromosome 12 was examined for ocular disease under general anesthesia. DNA samples from the patient and her family were used for molecular studies to determine the boundaries of the chromosome 12 deletion using polymorphic markers located on chromosome 12q21-q22. Results: The ocular abnormalities are consistent with a diagnosis of cornea plana, including a poor definition of the corneal limbus OU, microcornea (corneal diameter 9.25mm OD, and 9.50mm OS), flat irides and peripheral anterior synechiae. The intraocular pressures were normal (7 OD and 8 OS). The posterior segment exam showed small tilted optic nerves and a dull macular reflex. Systemic abnormalities included frontal bossing, low set ears and clinodactyly. Using polymorphic microsatellite markers located in the chromosome 12q21-q22 region, a 50 cM deletion (maximum size) was identified, with the proximal breakpoint between D12S329 (74cM) and D12S1709 (86cM) and the distal breakpoint between D12S84 (117cM) and D12S79(125cM). Included in this deletion is the gene responsible for autosomal recessive forms of cornea plana (keratocan) located at approximately 90cM. Conclusions: Cornea plana can be inherited as an autosomal recessive or autosomal dominant trait, and genetic loci for both the AD and AR forms have been mapped to chromosome 12q21-q22. Autosomal recessive forms of cornea plana are caused by mutations in the gene for keratocan, but this gene is not responsible for autosomal dominant forms of the disease. We have identified a patient with cornea plana who is hemizygous for the region of chromosome 12q21-q22 that contains the gene responsible for autosomal recessive forms of cornea plana (keratocan) and the locus for autosomal dominant cornea plana. Our results support the hypothesis that a gene responsible for autosomal dominant cornea plana is located within the 50 cM region deleted in this patient.

Keywords: genetics • anterior segment • cornea: basic science