自引率: 4.3%
被引量: 6016
通过率: 暂无数据
审稿周期: 2
版面费用: 暂无数据
国人发稿量: 45
投稿须知/期刊简介:
Published by Molecular Vision. ISSN: 1090-0535.<br /><br />Molecular Vision covers research in molecular biology, cell biology, and genetics of vision research. There is no published print counterpart to this multimedia peer reviewed journal.
期刊描述简介:
Published by Molecular Vision. ISSN: 1090-0535. Molecular Vision covers research in molecular biology, cell biology, and genetics of vision research. There is no published print counterpart to this multimedia peer reviewed journal.
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Macular corneal dystrophy types I and II are caused by distinct mutations in the CHST6 gene in Iceland.
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. 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. 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. 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.
被引量：- 发表：1970
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Mutations in corneal carbohydrate sulfotransferase 6 gene (CHST6) cause macular corneal dystrophy in Iceland.
Macular corneal dystrophy (MCD) is subdivided into three immunophenotypes (MCD types I, IA and II). Recently, mutations in the carbohydrate sulfotransferase 6 gene (CHST6) were identified to cause MCD. The purpose of this study was to examine CHST6 for mutations in Icelandic patients with MCD type I. Genomic DNA was extracted from leukocytes in the peripheral blood and the coding region of CHST6 was examined for mutations by polymerase chain reaction (PCR) and direct sequencing. Mutation analysis of the CHST6 coding region identified three different mutations in sixteen Icelandic patients with MCD type I. Eleven patients 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 mutations. One family with MCD type I contained a 10 base pair insertion (ATGCTGTGCG) between nucleotides 707 and 708. In this family, two affected siblings had a homozygous insertion while both their affected mother and their affected maternal aunt had a heterozygous insertion and a heterozygous C1075T mutation. Three different nucleotide changes were identified in the coding region of CHST6 in sixteen Icelandic patients with MCD type I. All three of these alterations are predicted to affect the translated protein and each of them corresponded to a particular disease haplotype that we had previously reported in this population.
被引量：- 发表：1970
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Physical and genetic mapping of the macular corneal dystrophy locus on chromosome 16q and exclusion of TAT and LCAT as candidate genes.
Macular corneal dystrophy (MCD) is an inherited autosomal recessive disorder that has been subdivided into three immunophenotypes, MCD types I, IA and II. We previously mapped the MCD type I gene to chromosome 16q22 and suggested that the MCD type II gene was linked to the same region. The purpose of this study was to construct a genomic contig spanning the MCD region and to narrow the MCD critical interval by haplotype analysis. The TAT and LCAT genes were mapped to determine if they might be the MCD gene. The MCD contig was constructed by screening YAC, PAC, and BAC libraries with microsatellite, STS and EST markers, employing a systematic "DNA walking" technique. Polymorphic markers mapped and ordered on the contig were used to screen the MCD affected individuals and their family members for haplotype analysis. Twenty-two YAC, 30 PAC, and 17 BAC clones were mapped to form the MCD contig. Markers mapped on the contig include 19 microsatellite, 14 STS, and 15 EST markers. Moreover, 18 novel STS markers were generated. Using the mapped and ordered microsatellite markers, haplotype analysis on 21 individuals with MCD type I or type II and their family members from Iceland narrowed the MCD interval to 3 overlapping PAC clones. In addition, the TAT and LCAT genes were mapped outside the MCD region. We established a genomic contig for the MCD region and dramatically narrowed the MCD critical interval. Mapping data show that the TAT and LCAT genes are not the cause of MCD.
被引量：- 发表：1970
