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Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis
BACKGROUND: Leber congenital amaurosis (LCA) is the earliest onset and most severe form of hereditary retinal dystrophy. So far, full spectrum of variations in the 15 genes known to cause LCA has not been systemically evaluated in East Asians. Therefore, we performed comprehensive detection of varia...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094346/ https://www.ncbi.nlm.nih.gov/pubmed/21602930 http://dx.doi.org/10.1371/journal.pone.0019458 |
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author | Li, Lin Xiao, Xueshan Li, Shiqiang Jia, Xiaoyun Wang, Panfeng Guo, Xiangming Jiao, Xiaodong Zhang, Qingjiong Hejtmancik, J. Fielding |
author_facet | Li, Lin Xiao, Xueshan Li, Shiqiang Jia, Xiaoyun Wang, Panfeng Guo, Xiangming Jiao, Xiaodong Zhang, Qingjiong Hejtmancik, J. Fielding |
author_sort | Li, Lin |
collection | PubMed |
description | BACKGROUND: Leber congenital amaurosis (LCA) is the earliest onset and most severe form of hereditary retinal dystrophy. So far, full spectrum of variations in the 15 genes known to cause LCA has not been systemically evaluated in East Asians. Therefore, we performed comprehensive detection of variants in these 15 genes in 87 unrelated Han Chinese patients with LCA. METHODOLOGY/PRINCIPAL FINDINGS: The 51 most frequently mutated exons and introns in the 15 genes were selected for an initial scan using cycle sequencing. All the remaining exons in 11 of the 15 genes were subsequently sequenced. Fifty-three different variants were identified in 44 of the 87 patients (50.6%), involving 78 of the 88 alleles (11 homozygous and 56 heterozygous variants). Of the 53 variants, 35 (66%) were novel pathogenic mutations. In these Chinese patients, variants in GUCY2D are the most common cause of LCA (16.1% cases), followed by CRB1 (11.5%), RPGRIP1 (8%), RPE65 (5.7%), SPATA7 (4.6%), CEP290 (4.6%), CRX (3.4%), LCA5 (2.3%), MERTK (2.3%), AIPL1 (1.1%), and RDH12 (1.1%). This differs from the variation spectrum described in other populations. An initial scan of 55 of 215 PCR amplicons, including 214 exons and 1 intron, detected 83.3% (65/78) of the mutant alleles ultimately found in these 87 patients. In addition, sequencing only 9 exons would detect over 50% of the identified variants and require less than 5% of the labor and cost of comprehensive sequencing for all exons. CONCLUSIONS/SIGNIFICANCE: Our results suggest that specific difference in the variation spectrum found in LCA patients from the Han Chinese and other populations are related by ethnicity. Sequencing exons in order of decreasing risk is a cost-effective way to identify causative mutations responsible for LCA, especially in the context of genetic counseling for individual patients in a clinical setting. |
format | Text |
id | pubmed-3094346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30943462011-05-19 Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis Li, Lin Xiao, Xueshan Li, Shiqiang Jia, Xiaoyun Wang, Panfeng Guo, Xiangming Jiao, Xiaodong Zhang, Qingjiong Hejtmancik, J. Fielding PLoS One Research Article BACKGROUND: Leber congenital amaurosis (LCA) is the earliest onset and most severe form of hereditary retinal dystrophy. So far, full spectrum of variations in the 15 genes known to cause LCA has not been systemically evaluated in East Asians. Therefore, we performed comprehensive detection of variants in these 15 genes in 87 unrelated Han Chinese patients with LCA. METHODOLOGY/PRINCIPAL FINDINGS: The 51 most frequently mutated exons and introns in the 15 genes were selected for an initial scan using cycle sequencing. All the remaining exons in 11 of the 15 genes were subsequently sequenced. Fifty-three different variants were identified in 44 of the 87 patients (50.6%), involving 78 of the 88 alleles (11 homozygous and 56 heterozygous variants). Of the 53 variants, 35 (66%) were novel pathogenic mutations. In these Chinese patients, variants in GUCY2D are the most common cause of LCA (16.1% cases), followed by CRB1 (11.5%), RPGRIP1 (8%), RPE65 (5.7%), SPATA7 (4.6%), CEP290 (4.6%), CRX (3.4%), LCA5 (2.3%), MERTK (2.3%), AIPL1 (1.1%), and RDH12 (1.1%). This differs from the variation spectrum described in other populations. An initial scan of 55 of 215 PCR amplicons, including 214 exons and 1 intron, detected 83.3% (65/78) of the mutant alleles ultimately found in these 87 patients. In addition, sequencing only 9 exons would detect over 50% of the identified variants and require less than 5% of the labor and cost of comprehensive sequencing for all exons. CONCLUSIONS/SIGNIFICANCE: Our results suggest that specific difference in the variation spectrum found in LCA patients from the Han Chinese and other populations are related by ethnicity. Sequencing exons in order of decreasing risk is a cost-effective way to identify causative mutations responsible for LCA, especially in the context of genetic counseling for individual patients in a clinical setting. Public Library of Science 2011-05-13 /pmc/articles/PMC3094346/ /pubmed/21602930 http://dx.doi.org/10.1371/journal.pone.0019458 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Li, Lin Xiao, Xueshan Li, Shiqiang Jia, Xiaoyun Wang, Panfeng Guo, Xiangming Jiao, Xiaodong Zhang, Qingjiong Hejtmancik, J. Fielding Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis |
title | Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis |
title_full | Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis |
title_fullStr | Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis |
title_full_unstemmed | Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis |
title_short | Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis |
title_sort | detection of variants in 15 genes in 87 unrelated chinese patients with leber congenital amaurosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094346/ https://www.ncbi.nlm.nih.gov/pubmed/21602930 http://dx.doi.org/10.1371/journal.pone.0019458 |
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