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Splice-site mutation causing partial retention of intron in the FLCN gene in Birt-Hogg-Dubé syndrome: a case report

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). Nearly 150 pathogenic mutations have been identified in FLCN. The most frequent pattern is a frameshift mutation within a coding exon. In addition, splice-site muta...

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Autores principales: Furuya, Mitsuko, Kobayashi, Hironori, Baba, Masaya, Ito, Takaaki, Tanaka, Reiko, Nakatani, Yukio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930857/
https://www.ncbi.nlm.nih.gov/pubmed/29720200
http://dx.doi.org/10.1186/s12920-018-0359-5
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author Furuya, Mitsuko
Kobayashi, Hironori
Baba, Masaya
Ito, Takaaki
Tanaka, Reiko
Nakatani, Yukio
author_facet Furuya, Mitsuko
Kobayashi, Hironori
Baba, Masaya
Ito, Takaaki
Tanaka, Reiko
Nakatani, Yukio
author_sort Furuya, Mitsuko
collection PubMed
description BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). Nearly 150 pathogenic mutations have been identified in FLCN. The most frequent pattern is a frameshift mutation within a coding exon. In addition, splice-site mutations have been reported, and previous studies have confirmed exon skipping in several cases. However, it is poorly understood whether there are any splice-site mutations that cause translation of intron regions in FLCN. CASE PRESENTATION: A 59-year-old Japanese patient with multiple pulmonary cysts and pneumothorax was hospitalized due to dyspnea. BHD was suspected and genetic testing was performed. The patient exhibited the splice-site mutation of FLCN in the 5′ end of intron 9 (c.1062 + 1G > A). Total mRNA was extracted from pulmonary cysts, and RT-PCR assessment and sequence analyses were done. Two distinct bands were generated; one was wild-type and the other was a larger-sized mutant. Sequence analysis of the latter transcript revealed the insertion of 130 base pairs of intron 9 from the beginning of the splice-site between exons 9 and 10. CONCLUSION: To our knowledge, this is the first report of distinct intron insertion using a BHD patient’s diseased tissue-derived mRNA. The present case suggests that a splice-site mutation can lead to exon skipping as well as intron reading mRNA. The splicing process may be dependent in part on whether the donor or acceptor site is affected. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12920-018-0359-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-59308572018-05-09 Splice-site mutation causing partial retention of intron in the FLCN gene in Birt-Hogg-Dubé syndrome: a case report Furuya, Mitsuko Kobayashi, Hironori Baba, Masaya Ito, Takaaki Tanaka, Reiko Nakatani, Yukio BMC Med Genomics Case Report BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). Nearly 150 pathogenic mutations have been identified in FLCN. The most frequent pattern is a frameshift mutation within a coding exon. In addition, splice-site mutations have been reported, and previous studies have confirmed exon skipping in several cases. However, it is poorly understood whether there are any splice-site mutations that cause translation of intron regions in FLCN. CASE PRESENTATION: A 59-year-old Japanese patient with multiple pulmonary cysts and pneumothorax was hospitalized due to dyspnea. BHD was suspected and genetic testing was performed. The patient exhibited the splice-site mutation of FLCN in the 5′ end of intron 9 (c.1062 + 1G > A). Total mRNA was extracted from pulmonary cysts, and RT-PCR assessment and sequence analyses were done. Two distinct bands were generated; one was wild-type and the other was a larger-sized mutant. Sequence analysis of the latter transcript revealed the insertion of 130 base pairs of intron 9 from the beginning of the splice-site between exons 9 and 10. CONCLUSION: To our knowledge, this is the first report of distinct intron insertion using a BHD patient’s diseased tissue-derived mRNA. The present case suggests that a splice-site mutation can lead to exon skipping as well as intron reading mRNA. The splicing process may be dependent in part on whether the donor or acceptor site is affected. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12920-018-0359-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-02 /pmc/articles/PMC5930857/ /pubmed/29720200 http://dx.doi.org/10.1186/s12920-018-0359-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Furuya, Mitsuko
Kobayashi, Hironori
Baba, Masaya
Ito, Takaaki
Tanaka, Reiko
Nakatani, Yukio
Splice-site mutation causing partial retention of intron in the FLCN gene in Birt-Hogg-Dubé syndrome: a case report
title Splice-site mutation causing partial retention of intron in the FLCN gene in Birt-Hogg-Dubé syndrome: a case report
title_full Splice-site mutation causing partial retention of intron in the FLCN gene in Birt-Hogg-Dubé syndrome: a case report
title_fullStr Splice-site mutation causing partial retention of intron in the FLCN gene in Birt-Hogg-Dubé syndrome: a case report
title_full_unstemmed Splice-site mutation causing partial retention of intron in the FLCN gene in Birt-Hogg-Dubé syndrome: a case report
title_short Splice-site mutation causing partial retention of intron in the FLCN gene in Birt-Hogg-Dubé syndrome: a case report
title_sort splice-site mutation causing partial retention of intron in the flcn gene in birt-hogg-dubé syndrome: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930857/
https://www.ncbi.nlm.nih.gov/pubmed/29720200
http://dx.doi.org/10.1186/s12920-018-0359-5
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