Macular corneal dystrophy types I and II are caused by distinctmutations in the CHST6 gene in Iceland

[摘要] Purpose: To identify CHST6 mutations in five additionalIcelandic cases of macular corneal dystrophy (MCD) type I and in fourfamilies with MCD type II from Iceland.Methods: Genomic DNA was extracted from blood leukocytes of patientswith MCD, their healthy family members, and from control individuals.CHST6 mutations were determined by PCR-sequencing. Immunophenotypesof MCD were determined by measuring antigenic keratan sulfate (AgKS)levels in serum and by an immunohistochemical study on corneal tissue.Results: Five additional cases of MCD type I and four families withMCD type II from Iceland were studied. A homozygous p.A128V mutation inthe coding region of the CHST6 gene was identified in four of thefive MCD type I cases. The other person with MCD type I was a compoundheterozygote for p.A128V and a frameshift p.V6fs resulting from a10-base pair insertion (c.15_16insATGCTGTGCG). Four of five individualswith MCD type II were compound heterozygotes for p.A128V and p.V329L,thus sharing the same p.A128V mutation as MCD type I. One patient withMCD type II was homozygous for p.V329L. The p.V329L mutation was onlyfound in MCD type II patients. An analysis of the upstream region ofCHST6 disclosed no upstream deletion or replacements in Icelandicpatients with MCD type II.Conclusions: The findings fit the haplotype analysis that wereported previously in Icelandic MCD families and indicate thatdifferent mutations in CHST6 cause MCD type I and type II inIceland.

[学科分类] 生物化学/生物物理