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Molecular analysis of the CHST6 gene in Korean patients with macular corneal dystrophy: Identification of three novel mutations

PURPOSE: To identify the underlying genetic defect in Korean patients with macular corneal dystrophy (MCD). METHODS: Genomic DNA was isolated from peripheral blood leukocytes of seven patients from six unrelated families with MCD (three men and four women). Polymerase chain reaction was performed fo...

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Autores principales: Park, Shin Hae, Ahn, Ye Jin, Chae, Hyojin, Kim, Yonggoo, Kim, Man Soo, Kim, Myungshin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626780/
https://www.ncbi.nlm.nih.gov/pubmed/26604660
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author Park, Shin Hae
Ahn, Ye Jin
Chae, Hyojin
Kim, Yonggoo
Kim, Man Soo
Kim, Myungshin
author_facet Park, Shin Hae
Ahn, Ye Jin
Chae, Hyojin
Kim, Yonggoo
Kim, Man Soo
Kim, Myungshin
author_sort Park, Shin Hae
collection PubMed
description PURPOSE: To identify the underlying genetic defect in Korean patients with macular corneal dystrophy (MCD). METHODS: Genomic DNA was isolated from peripheral blood leukocytes of seven patients from six unrelated families with MCD (three men and four women). Polymerase chain reaction was performed for coding regions of the carbohydrate sulfotransferase (CHST6), gene followed by bidirectional sequencing. Targeted mutational analysis (exons 4, 11–12, 14) of the transforming growth factor, beta-induced (TGFBI) gene was performed for all patients. RESULTS: All seven patients were found to have compound heterozygous mutations in the CHST6 gene. In addition to six previously reported mutations, c.95C>A (p.Ser32*), c.521A>G (p.Lys174Arg), c.557C>G (p.Pro186Arg), c.613C>T (p.Arg205Trp), c.820G>A (p.Glu274Lys), and c.1072T>C (p.Tyr358His), three novel mutations were identified in this study, including two missense mutations, c.353C>T (p.Ser118Phe) and c.922C>T (p.His308Tyr), and one frameshift mutation, c.786delC (p.L264Cfs*117). Among the three novel mutations, only the c.353C>T mutation had been reported in the Exon Aggregation Consortium database at an extremely low frequency of 0.00005072. In addition, these three novel mutations were absent from controls in 1,000 genomes, dbSNP, and the TIARA genome database, which is a Korean personal genome database. The most frequent mutation was c.613C>T (p.Arg205Trp), revealed in four unrelated Korean families, which has not previously been reported in other populations. No mutations were detected in the TGFBI gene. DISCUSSION: This is the first report on genetic analysis of Korean MCD patients. Three novel and six previously reported disease-causing CHST6 mutations were identified, which expands the mutational spectrum of MCD.
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spelling pubmed-46267802015-11-24 Molecular analysis of the CHST6 gene in Korean patients with macular corneal dystrophy: Identification of three novel mutations Park, Shin Hae Ahn, Ye Jin Chae, Hyojin Kim, Yonggoo Kim, Man Soo Kim, Myungshin Mol Vis Research Article PURPOSE: To identify the underlying genetic defect in Korean patients with macular corneal dystrophy (MCD). METHODS: Genomic DNA was isolated from peripheral blood leukocytes of seven patients from six unrelated families with MCD (three men and four women). Polymerase chain reaction was performed for coding regions of the carbohydrate sulfotransferase (CHST6), gene followed by bidirectional sequencing. Targeted mutational analysis (exons 4, 11–12, 14) of the transforming growth factor, beta-induced (TGFBI) gene was performed for all patients. RESULTS: All seven patients were found to have compound heterozygous mutations in the CHST6 gene. In addition to six previously reported mutations, c.95C>A (p.Ser32*), c.521A>G (p.Lys174Arg), c.557C>G (p.Pro186Arg), c.613C>T (p.Arg205Trp), c.820G>A (p.Glu274Lys), and c.1072T>C (p.Tyr358His), three novel mutations were identified in this study, including two missense mutations, c.353C>T (p.Ser118Phe) and c.922C>T (p.His308Tyr), and one frameshift mutation, c.786delC (p.L264Cfs*117). Among the three novel mutations, only the c.353C>T mutation had been reported in the Exon Aggregation Consortium database at an extremely low frequency of 0.00005072. In addition, these three novel mutations were absent from controls in 1,000 genomes, dbSNP, and the TIARA genome database, which is a Korean personal genome database. The most frequent mutation was c.613C>T (p.Arg205Trp), revealed in four unrelated Korean families, which has not previously been reported in other populations. No mutations were detected in the TGFBI gene. DISCUSSION: This is the first report on genetic analysis of Korean MCD patients. Three novel and six previously reported disease-causing CHST6 mutations were identified, which expands the mutational spectrum of MCD. Molecular Vision 2015-10-26 /pmc/articles/PMC4626780/ /pubmed/26604660 Text en Copyright © 2015 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Park, Shin Hae
Ahn, Ye Jin
Chae, Hyojin
Kim, Yonggoo
Kim, Man Soo
Kim, Myungshin
Molecular analysis of the CHST6 gene in Korean patients with macular corneal dystrophy: Identification of three novel mutations
title Molecular analysis of the CHST6 gene in Korean patients with macular corneal dystrophy: Identification of three novel mutations
title_full Molecular analysis of the CHST6 gene in Korean patients with macular corneal dystrophy: Identification of three novel mutations
title_fullStr Molecular analysis of the CHST6 gene in Korean patients with macular corneal dystrophy: Identification of three novel mutations
title_full_unstemmed Molecular analysis of the CHST6 gene in Korean patients with macular corneal dystrophy: Identification of three novel mutations
title_short Molecular analysis of the CHST6 gene in Korean patients with macular corneal dystrophy: Identification of three novel mutations
title_sort molecular analysis of the chst6 gene in korean patients with macular corneal dystrophy: identification of three novel mutations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626780/
https://www.ncbi.nlm.nih.gov/pubmed/26604660
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