Novel Mutations in the CHST6 Gene Associated with Macular Corneal Dystrophy in American Patients

Abstract

Abstract: : Purpose: To further characterize the role of the CHST6 gene in macular corneal dystrophy (MCD) through identification of causative mutations in a cohort of affected patients from the United States. Methods: Genomic DNA was extracted from buccal epithelium of 16 patients (14 families) with MCD, as well as 15 unaffected relatives and 78 healthy controls. The coding region of the CHST6 gene was evaluated by PCR amplification and direct sequencing. Subtyping of MCD into types I and II was performed by measuring serum levels of antigenic keratan sulfate. Results: Analysis of the CHST6 coding region of patients with type I MCD identified: 8 novel compound heterozygous missense mutations (Ser51Leu, Trp77Cys, Arg93Ser, Val99Asp, Cys102Gly, Tyr110Cys, Arg162Gly, Leu276Pro); 1 previously described compound heterozygous missense mutation (Leu200Arg); 1 novel homozygous nonsense mutation (Gln331Stop); and 1 novel heterozygous frameshift mutation (1752Insertion(GTGCGCTG)). None of these nucleotide changes was identified in the control patients. Promoter region mutations were not detected using junction PCR in the four patients (four families) identified as having type II MCD. Conclusions: A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I MCD in affected Caucasian patients in the United States. The multiple novel coding region mutations found in this population of affected American patients, in addition to the multiple mutations founds in MCD patients from other populations, are in contrast to the conserved number of mutations associated with the ßig-h3 corneal dystrophies.

Keywords: cornea: stroma and keratocytes • genetics • mutations