PURPOSE: To identify CHST6 mutations in five additional Icelandic cases of macular corneal dystrophy (MCD) type I and in four families with MCD type II from Iceland. METHODS: Genomic DNA was extracted from blood leukocytes of patients with MCD, their healthy family members, and from control individuals. CHST6 mutations were determined by PCR-sequencing. Immunophenotypes of 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 with MCD type II from Iceland were studied. A homozygous p.A128V mutation in the coding region of the CHST6 gene was identified in four of the five MCD type I cases. The other person with MCD type I was a compound heterozygote for p.A128V and a frameshift p.V6fs resulting from a 10-base pair insertion (c.15_16insATGCTGTGCG). Four of five individuals with 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 with MCD type II was homozygous for p.V329L. The p.V329L mutation was only found in MCD type II patients. An analysis of the upstream region of CHST6 disclosed no upstream deletion or replacements in Icelandic patients with MCD type II. CONCLUSIONS: The findings fit the haplotype analysis that we reported previously in Icelandic MCD families and indicate that different mutations in CHST6 cause MCD type I and type II in Iceland.
PURPOSE: To identify CHST6 mutations in five additional Icelandic cases of macular corneal dystrophy (MCD) type I and in four families with MCD type II from Iceland. METHODS: Genomic DNA was extracted from blood leukocytes of patients with MCD, their healthy family members, and from control individuals. CHST6 mutations were determined by PCR-sequencing. Immunophenotypes of 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 with MCD type II from Iceland were studied. A homozygous p.A128V mutation in the coding region of the CHST6 gene was identified in four of the five MCD type I cases. The other person with MCD type I was a compound heterozygote for p.A128V and a frameshift p.V6fs resulting from a 10-base pair insertion (c.15_16insATGCTGTGCG). Four of five individuals with 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 with MCD type II was homozygous for p.V329L. The p.V329L mutation was only found in MCD type IIpatients. An analysis of the upstream region of CHST6 disclosed no upstream deletion or replacements in Icelandic patients with MCD type II. CONCLUSIONS: The findings fit the haplotype analysis that we reported previously in Icelandic MCD families and indicate that different mutations in CHST6 cause MCD type I and type II in Iceland.
Authors: Jayne S Weiss; H U Møller; Walter Lisch; Shigeru Kinoshita; Anthony J Aldave; Michael W Belin; Tero Kivelä; Massimo Busin; Francis L Munier; Berthold Seitz; John Sutphin; Cecilie Bredrup; Mark J Mannis; Christopher J Rapuano; Gabriel Van Rij; Eung Kweon Kim; Gordon K Klintworth Journal: Cornea Date: 2008-12 Impact factor: 2.651
Authors: Nadia Carstens; Susan Williams; Saadiah Goolam; Trevor Carmichael; Ming Sin Cheung; Stine Büchmann-Møller; Marc Sultan; Frank Staedtler; Chao Zou; Peter Swart; Dennis S Rice; Arnaud Lacoste; Kim Paes; Michèle Ramsay Journal: BMC Med Genet Date: 2016-07-20 Impact factor: 2.103
Authors: Afia Sultana; Gordon K Klintworth; Eugene J-M A Thonar; Geeta K Vemuganti; Chitra Kannabiran Journal: Mol Vis Date: 2009-02-09 Impact factor: 2.367