Mutations in corneal carbohydrate sulfotransferase 6 gene (CHST6) cause macular corneal dystrophy in Iceland

PURPOSE: Macular corneal dystrophy (MCD) is subdivided into three immunophe notypes (MCD types I, IA and II). Recently, mutations in the carbohydrate s ulfotransferase 6 gene (CHST6) were identified to cause MCD. The purpose of this study was to examine CHST6 for mutations in Icelandic patients with M CD type I. METHODS: Genomic DNA was extracted from leukocytes in the peripheral blood and the coding region of CHST6 was examined for mutations by polymerase cha in reaction (PCR) and direct sequencing. RESULTS: Mutation analysis of the CHST6 coding region identified three diff erent mutations in sixteen Icelandic patients with MCD type I. Eleven patie nts with MCD type I were homozygous for a C1075T mutation. One patient with MCD type I was found to be a compound heterozygous for C1075T and G1189C m utations. One family with MCD type I contained a 10 base pair insertion (AT GCTGTGCG) between nucleotides 707 and 708. In this family, two affected sib lings had a homozygous insertion while both their affected mother and their affected maternal aunt had a heterozygous insertion and a heterozygous C10 75T mutation. CONCLUSIONS: Three different nucleotide changes were identified in the codi ng region of CHST6 in sixteen Icelandic patients with MCD type I. All three of these alterations are predicted to affect the translated protein and ea ch of them corresponded to a particular disease haplotype that we had previ ously reported in this population.