Cargando…
Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing
Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198027/ https://www.ncbi.nlm.nih.gov/pubmed/34070492 http://dx.doi.org/10.3390/ijms22115594 |
_version_ | 1783707039799705600 |
---|---|
author | Lin, Ting-Yi Chang, Yun-Chia Hsiao, Yu-Jer Chien, Yueh Jheng, Ying-Chun Wu, Jing-Rong Ching, Lo-Jei Hwang, De-Kuang Hsu, Chih-Chien Lin, Tai-Chi Chou, Yu-Bai Huang, Yi-Ming Chen, Shih-Jen Yang, Yi-Ping Tsai, Ping-Hsing |
author_facet | Lin, Ting-Yi Chang, Yun-Chia Hsiao, Yu-Jer Chien, Yueh Jheng, Ying-Chun Wu, Jing-Rong Ching, Lo-Jei Hwang, De-Kuang Hsu, Chih-Chien Lin, Tai-Chi Chou, Yu-Bai Huang, Yi-Ming Chen, Shih-Jen Yang, Yi-Ping Tsai, Ping-Hsing |
author_sort | Lin, Ting-Yi |
collection | PubMed |
description | Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver genes, disease-causing variants, and retinitis pigmentosa (RP)-associated pathways. Using family-based whole-exome sequencing (WES) to identify putative RP-causing rare variants, we identified a total of five potentially pathogenic variants located in genes OR56A5, OR52L1, CTSD, PRF1, KBTBD13, and ATP2B4. Of the variants present in all affected individuals, genes OR56A5, OR52L1, CTSD, KBTBD13, and ATP2B4 present as missense mutations, while PRF1 and CTSD present as frameshift variants. Sanger sequencing confirmed the presence of the novel pathogenic variant PRF1 (c.124_128del) that has not been reported previously. More causal-effect or evidence-based studies will be required to elucidate the precise roles of these SNPs in the RP pathogenesis. Taken together, our findings may allow us to explore the risk variants based on the sequencing data and upgrade the existing variant annotation database in Taiwan. It may help detect specific eye diseases such as retinitis pigmentosa in East Asia. |
format | Online Article Text |
id | pubmed-8198027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81980272021-06-14 Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing Lin, Ting-Yi Chang, Yun-Chia Hsiao, Yu-Jer Chien, Yueh Jheng, Ying-Chun Wu, Jing-Rong Ching, Lo-Jei Hwang, De-Kuang Hsu, Chih-Chien Lin, Tai-Chi Chou, Yu-Bai Huang, Yi-Ming Chen, Shih-Jen Yang, Yi-Ping Tsai, Ping-Hsing Int J Mol Sci Article Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver genes, disease-causing variants, and retinitis pigmentosa (RP)-associated pathways. Using family-based whole-exome sequencing (WES) to identify putative RP-causing rare variants, we identified a total of five potentially pathogenic variants located in genes OR56A5, OR52L1, CTSD, PRF1, KBTBD13, and ATP2B4. Of the variants present in all affected individuals, genes OR56A5, OR52L1, CTSD, KBTBD13, and ATP2B4 present as missense mutations, while PRF1 and CTSD present as frameshift variants. Sanger sequencing confirmed the presence of the novel pathogenic variant PRF1 (c.124_128del) that has not been reported previously. More causal-effect or evidence-based studies will be required to elucidate the precise roles of these SNPs in the RP pathogenesis. Taken together, our findings may allow us to explore the risk variants based on the sequencing data and upgrade the existing variant annotation database in Taiwan. It may help detect specific eye diseases such as retinitis pigmentosa in East Asia. MDPI 2021-05-25 /pmc/articles/PMC8198027/ /pubmed/34070492 http://dx.doi.org/10.3390/ijms22115594 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lin, Ting-Yi Chang, Yun-Chia Hsiao, Yu-Jer Chien, Yueh Jheng, Ying-Chun Wu, Jing-Rong Ching, Lo-Jei Hwang, De-Kuang Hsu, Chih-Chien Lin, Tai-Chi Chou, Yu-Bai Huang, Yi-Ming Chen, Shih-Jen Yang, Yi-Ping Tsai, Ping-Hsing Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing |
title | Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing |
title_full | Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing |
title_fullStr | Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing |
title_full_unstemmed | Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing |
title_short | Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing |
title_sort | identification of novel genomic-variant patterns of or56a5, or52l1, and ctsd in retinitis pigmentosa patients by whole-exome sequencing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198027/ https://www.ncbi.nlm.nih.gov/pubmed/34070492 http://dx.doi.org/10.3390/ijms22115594 |
work_keys_str_mv | AT lintingyi identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT changyunchia identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT hsiaoyujer identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT chienyueh identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT jhengyingchun identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT wujingrong identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT chinglojei identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT hwangdekuang identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT hsuchihchien identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT lintaichi identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT chouyubai identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT huangyiming identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT chenshihjen identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT yangyiping identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing AT tsaipinghsing identificationofnovelgenomicvariantpatternsofor56a5or52l1andctsdinretinitispigmentosapatientsbywholeexomesequencing |