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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2018
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.
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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
title_full Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B
title_fullStr Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B
title_full_unstemmed Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B
title_short Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B
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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