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Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B
Liddle syndrome (LS), a monogenetic autosomal dominant disorder, is mainly characterized by early-onset hypertension and hypokalemia. Clinically, misdiagnosis or missing diagnosis is common, since clinical phenotypes of LS are variable and nonspecific. We report a family with misdiagnosis of primary...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bioscientifica Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311463/ https://www.ncbi.nlm.nih.gov/pubmed/30496127 http://dx.doi.org/10.1530/EC-18-0484 |
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author | Fan, Peng Lu, Chao-Xia Zhang, Di Yang, Kun-Qi Lu, Pei-Pei Zhang, Ying Meng, Xu Hao, Su-Fang Luo, Fang Liu, Ya-Xin Zhang, Hui-Min Song, Lei Cai, Jun Zhang, Xue Zhou, Xian-Liang |
author_facet | Fan, Peng Lu, Chao-Xia Zhang, Di Yang, Kun-Qi Lu, Pei-Pei Zhang, Ying Meng, Xu Hao, Su-Fang Luo, Fang Liu, Ya-Xin Zhang, Hui-Min Song, Lei Cai, Jun Zhang, Xue Zhou, Xian-Liang |
author_sort | Fan, Peng |
collection | PubMed |
description | Liddle syndrome (LS), a monogenetic autosomal dominant disorder, is mainly characterized by early-onset hypertension and hypokalemia. Clinically, misdiagnosis or missing diagnosis is common, since clinical phenotypes of LS are variable and nonspecific. We report a family with misdiagnosis of primary aldosteronism (PA), but identify as LS with a pathogenic frameshift mutation of the epithelial sodium channel (ENaC) β subunit. DNA samples were collected from a 32-year-old proband and 31 other relatives in the same family. A designed panel including 41 genes associated with monogenic hypertension was screened using next-generation sequencing. The best candidate disease-causing variants were verified by Sanger sequencing. Genetic analysis of the proband revealed a novel frameshift mutation c.1838delC (p.Pro613Glnfs*675) in exon 13 of SCNN1B. This heterozygous mutation involved the deletion of a cytosine from a string of three consecutive cytosines located at codons 612 to 613 and resulted in deletion of the crucial PY motif and elongation of the β-ENaC protein. The identical mutation was also found in 12 affected family members. Amiloride was effective in alleviating LS for patients. There were no SCNN1A or SCNN1G mutations in this family. Our study emphasizes the importance of considering LS in the differential diagnosis of early-onset hypertension. The identification of a novel frameshift mutation of SCNN1B enriches the genetic spectrum of LS and has allowed treatment of this affected family to prevent severe complications. |
format | Online Article Text |
id | pubmed-6311463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Bioscientifica Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-63114632019-01-03 Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B Fan, Peng Lu, Chao-Xia Zhang, Di Yang, Kun-Qi Lu, Pei-Pei Zhang, Ying Meng, Xu Hao, Su-Fang Luo, Fang Liu, Ya-Xin Zhang, Hui-Min Song, Lei Cai, Jun Zhang, Xue Zhou, Xian-Liang Endocr Connect Research Liddle syndrome (LS), a monogenetic autosomal dominant disorder, is mainly characterized by early-onset hypertension and hypokalemia. Clinically, misdiagnosis or missing diagnosis is common, since clinical phenotypes of LS are variable and nonspecific. We report a family with misdiagnosis of primary aldosteronism (PA), but identify as LS with a pathogenic frameshift mutation of the epithelial sodium channel (ENaC) β subunit. DNA samples were collected from a 32-year-old proband and 31 other relatives in the same family. A designed panel including 41 genes associated with monogenic hypertension was screened using next-generation sequencing. The best candidate disease-causing variants were verified by Sanger sequencing. Genetic analysis of the proband revealed a novel frameshift mutation c.1838delC (p.Pro613Glnfs*675) in exon 13 of SCNN1B. This heterozygous mutation involved the deletion of a cytosine from a string of three consecutive cytosines located at codons 612 to 613 and resulted in deletion of the crucial PY motif and elongation of the β-ENaC protein. The identical mutation was also found in 12 affected family members. Amiloride was effective in alleviating LS for patients. There were no SCNN1A or SCNN1G mutations in this family. Our study emphasizes the importance of considering LS in the differential diagnosis of early-onset hypertension. The identification of a novel frameshift mutation of SCNN1B enriches the genetic spectrum of LS and has allowed treatment of this affected family to prevent severe complications. Bioscientifica Ltd 2018-11-28 /pmc/articles/PMC6311463/ /pubmed/30496127 http://dx.doi.org/10.1530/EC-18-0484 Text en © 2018 The authors http://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Research Fan, Peng Lu, Chao-Xia Zhang, Di Yang, Kun-Qi Lu, Pei-Pei Zhang, Ying Meng, Xu Hao, Su-Fang Luo, Fang Liu, Ya-Xin Zhang, Hui-Min Song, Lei Cai, Jun Zhang, Xue Zhou, Xian-Liang Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B |
title | Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B
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title_full | Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B
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title_fullStr | Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B
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title_full_unstemmed | Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B
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title_short | Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B
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title_sort | liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of scnn1b |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311463/ https://www.ncbi.nlm.nih.gov/pubmed/30496127 http://dx.doi.org/10.1530/EC-18-0484 |
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