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Molecular Diagnosis of Putative Stargardt Disease by Capture Next Generation Sequencing

Stargardt Disease (STGD) is the commonest genetic form of juvenile or early adult onset macular degeneration, which is a genetically heterogeneous disease. Molecular diagnosis of STGD remains a challenge in a significant proportion of cases. To address this, seven patients from five putative STGD fa...

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Autores principales: Zhang, Xiao, Ge, Xianglian, Shi, Wei, Huang, Ping, Min, Qingjie, Li, Minghan, Yu, Xinping, Wu, Yaming, Zhao, Guangyu, Tong, Yi, Jin, Zi-Bing, Qu, Jia, Gu, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999032/
https://www.ncbi.nlm.nih.gov/pubmed/24763286
http://dx.doi.org/10.1371/journal.pone.0095528
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author Zhang, Xiao
Ge, Xianglian
Shi, Wei
Huang, Ping
Min, Qingjie
Li, Minghan
Yu, Xinping
Wu, Yaming
Zhao, Guangyu
Tong, Yi
Jin, Zi-Bing
Qu, Jia
Gu, Feng
author_facet Zhang, Xiao
Ge, Xianglian
Shi, Wei
Huang, Ping
Min, Qingjie
Li, Minghan
Yu, Xinping
Wu, Yaming
Zhao, Guangyu
Tong, Yi
Jin, Zi-Bing
Qu, Jia
Gu, Feng
author_sort Zhang, Xiao
collection PubMed
description Stargardt Disease (STGD) is the commonest genetic form of juvenile or early adult onset macular degeneration, which is a genetically heterogeneous disease. Molecular diagnosis of STGD remains a challenge in a significant proportion of cases. To address this, seven patients from five putative STGD families were recruited. We performed capture next generation sequencing (CNGS) of the probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Seven disease-causing mutations in ABCA4 and two in PROM1 were identified by CNGS, which provides a confident genetic diagnosis in these five families. We also provided a genetic basis to explain the differences among putative STGD due to various mutations in different genes. Meanwhile, we show for the first time that compound heterozygous mutations in PROM1 gene could cause cone-rod dystrophy. Our findings support the enormous potential of CNGS in putative STGD molecular diagnosis.
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spelling pubmed-39990322014-04-29 Molecular Diagnosis of Putative Stargardt Disease by Capture Next Generation Sequencing Zhang, Xiao Ge, Xianglian Shi, Wei Huang, Ping Min, Qingjie Li, Minghan Yu, Xinping Wu, Yaming Zhao, Guangyu Tong, Yi Jin, Zi-Bing Qu, Jia Gu, Feng PLoS One Research Article Stargardt Disease (STGD) is the commonest genetic form of juvenile or early adult onset macular degeneration, which is a genetically heterogeneous disease. Molecular diagnosis of STGD remains a challenge in a significant proportion of cases. To address this, seven patients from five putative STGD families were recruited. We performed capture next generation sequencing (CNGS) of the probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Seven disease-causing mutations in ABCA4 and two in PROM1 were identified by CNGS, which provides a confident genetic diagnosis in these five families. We also provided a genetic basis to explain the differences among putative STGD due to various mutations in different genes. Meanwhile, we show for the first time that compound heterozygous mutations in PROM1 gene could cause cone-rod dystrophy. Our findings support the enormous potential of CNGS in putative STGD molecular diagnosis. Public Library of Science 2014-04-24 /pmc/articles/PMC3999032/ /pubmed/24763286 http://dx.doi.org/10.1371/journal.pone.0095528 Text en © 2014 Zhang et al http://creativecommons.org/licenses/by/4.0/ 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 author and source are properly credited.
spellingShingle Research Article
Zhang, Xiao
Ge, Xianglian
Shi, Wei
Huang, Ping
Min, Qingjie
Li, Minghan
Yu, Xinping
Wu, Yaming
Zhao, Guangyu
Tong, Yi
Jin, Zi-Bing
Qu, Jia
Gu, Feng
Molecular Diagnosis of Putative Stargardt Disease by Capture Next Generation Sequencing
title Molecular Diagnosis of Putative Stargardt Disease by Capture Next Generation Sequencing
title_full Molecular Diagnosis of Putative Stargardt Disease by Capture Next Generation Sequencing
title_fullStr Molecular Diagnosis of Putative Stargardt Disease by Capture Next Generation Sequencing
title_full_unstemmed Molecular Diagnosis of Putative Stargardt Disease by Capture Next Generation Sequencing
title_short Molecular Diagnosis of Putative Stargardt Disease by Capture Next Generation Sequencing
title_sort molecular diagnosis of putative stargardt disease by capture next generation sequencing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999032/
https://www.ncbi.nlm.nih.gov/pubmed/24763286
http://dx.doi.org/10.1371/journal.pone.0095528
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