A Novel Frame-Shift Mutation in SCNN1B Identified in a Chinese Family Characterized by Early-Onset Hypertension
BackgroundLiddle syndrome is a form of monogenic hypertension caused by mutations in the three homologous subunits of the epithelial sodium channels (ENaCs), α, β, and γ. It is characterized by early-onset refractory hypertension, hypokalemia, low renin activity, and hypoaldosteronism. In this study...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.896564/full |
| _version_ | 1818546769473044480 |
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| author | Yi-Ting Lu Xin-Chang Liu Ze-Ming Zhou Di Zhang Lin Sun Ying Zhang Peng Fan Lin Zhang Ya-Xin Liu Fang Luo Xian-Liang Zhou |
| author_facet | Yi-Ting Lu Xin-Chang Liu Ze-Ming Zhou Di Zhang Lin Sun Ying Zhang Peng Fan Lin Zhang Ya-Xin Liu Fang Luo Xian-Liang Zhou |
| author_sort | Yi-Ting Lu |
| collection | DOAJ |
| description | BackgroundLiddle syndrome is a form of monogenic hypertension caused by mutations in the three homologous subunits of the epithelial sodium channels (ENaCs), α, β, and γ. It is characterized by early-onset refractory hypertension, hypokalemia, low renin activity, and hypoaldosteronism. In this study, we report a novel frame-shift mutation in SCNN1B responsible for Liddle syndrome in a Chinese family.MethodsDNA samples were collected from all participants. Whole-exome sequencing was performed in the proband to detect possible causative variants. Sanger sequencing was then conducted in the other family members to verify the candidate variant, and in 100 patients with hypertension and 100 normotensive controls to exclude population genetic polymorphism.ResultsWe identified a novel frame-shift mutation (c.1691_1693delinsG) in SCNN1B that was responsible for Liddle syndrome in this family. This mutation leads to the substitution of Arg in place of Gln at codon site 564 and generates a new stop codon at 592, influencing the crucial PY motif and resulting in reduced inactivation of the ENaCs. Aside from the proband, eight family members carried the mutation. Intra-familial phenotypic heterogeneity was observed in the blood pressure and serum potassium levels. Amiloride therapy combined with a low sodium diet is effective to alleviate the symptoms of patients with Liddle syndrome.Conclusionc.1691_1693delinsG, a novel frame-shift mutation in the β subunit of ENaC, was identified in a Chinese family with Liddle syndrome by whole-exome sequencing. Phenotypic heterogeneity can make diagnosis of Liddle syndrome difficult on the basis of clinical or biochemical characteristics alone. Genetic analysis is a useful tool allowing timely and accurate diagnosis of Liddle syndrome and playing a guiding role in precise treatment of the disease. |
| first_indexed | 2024-12-12T07:57:40Z |
| format | Article |
| id | doaj.art-59143b1187f544ca81a2d52236f202aa |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-12T07:57:40Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-59143b1187f544ca81a2d52236f202aa2022-12-22T00:32:16ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-06-01910.3389/fcvm.2022.896564896564A Novel Frame-Shift Mutation in SCNN1B Identified in a Chinese Family Characterized by Early-Onset HypertensionYi-Ting Lu0Xin-Chang Liu1Ze-Ming Zhou2Di Zhang3Lin Sun4Ying Zhang5Peng Fan6Lin Zhang7Ya-Xin Liu8Fang Luo9Xian-Liang Zhou10Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaEmergency and Critical Care Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackgroundLiddle syndrome is a form of monogenic hypertension caused by mutations in the three homologous subunits of the epithelial sodium channels (ENaCs), α, β, and γ. It is characterized by early-onset refractory hypertension, hypokalemia, low renin activity, and hypoaldosteronism. In this study, we report a novel frame-shift mutation in SCNN1B responsible for Liddle syndrome in a Chinese family.MethodsDNA samples were collected from all participants. Whole-exome sequencing was performed in the proband to detect possible causative variants. Sanger sequencing was then conducted in the other family members to verify the candidate variant, and in 100 patients with hypertension and 100 normotensive controls to exclude population genetic polymorphism.ResultsWe identified a novel frame-shift mutation (c.1691_1693delinsG) in SCNN1B that was responsible for Liddle syndrome in this family. This mutation leads to the substitution of Arg in place of Gln at codon site 564 and generates a new stop codon at 592, influencing the crucial PY motif and resulting in reduced inactivation of the ENaCs. Aside from the proband, eight family members carried the mutation. Intra-familial phenotypic heterogeneity was observed in the blood pressure and serum potassium levels. Amiloride therapy combined with a low sodium diet is effective to alleviate the symptoms of patients with Liddle syndrome.Conclusionc.1691_1693delinsG, a novel frame-shift mutation in the β subunit of ENaC, was identified in a Chinese family with Liddle syndrome by whole-exome sequencing. Phenotypic heterogeneity can make diagnosis of Liddle syndrome difficult on the basis of clinical or biochemical characteristics alone. Genetic analysis is a useful tool allowing timely and accurate diagnosis of Liddle syndrome and playing a guiding role in precise treatment of the disease.https://www.frontiersin.org/articles/10.3389/fcvm.2022.896564/fullLiddle syndromeframe-shift mutationSCNN1Bmonogenic hypertensiongenetic testing |
| spellingShingle | Yi-Ting Lu Xin-Chang Liu Ze-Ming Zhou Di Zhang Lin Sun Ying Zhang Peng Fan Lin Zhang Ya-Xin Liu Fang Luo Xian-Liang Zhou A Novel Frame-Shift Mutation in SCNN1B Identified in a Chinese Family Characterized by Early-Onset Hypertension Frontiers in Cardiovascular Medicine Liddle syndrome frame-shift mutation SCNN1B monogenic hypertension genetic testing |
| title | A Novel Frame-Shift Mutation in SCNN1B Identified in a Chinese Family Characterized by Early-Onset Hypertension |
| title_full | A Novel Frame-Shift Mutation in SCNN1B Identified in a Chinese Family Characterized by Early-Onset Hypertension |
| title_fullStr | A Novel Frame-Shift Mutation in SCNN1B Identified in a Chinese Family Characterized by Early-Onset Hypertension |
| title_full_unstemmed | A Novel Frame-Shift Mutation in SCNN1B Identified in a Chinese Family Characterized by Early-Onset Hypertension |
| title_short | A Novel Frame-Shift Mutation in SCNN1B Identified in a Chinese Family Characterized by Early-Onset Hypertension |
| title_sort | novel frame shift mutation in scnn1b identified in a chinese family characterized by early onset hypertension |
| topic | Liddle syndrome frame-shift mutation SCNN1B monogenic hypertension genetic testing |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.896564/full |
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