-
Je něco špatně v tomto záznamu ?
A novel nonsense mutation in the β-subunit of the epithelial sodium channel causing Liddle syndrome
Š. Mareš, J. Filipovský, K. Vlková, M. Pešta, V. Černá, J. Hrabák, J. Mlíková Seidlerová, O. Mayer
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
ROAD: Directory of Open Access Scholarly Resources od 1992
Odkazy
PubMed
34223773
DOI
10.1080/08037051.2021.1942785
Knihovny.cz E-zdroje
- MeSH
- epiteliální sodíkový kanál genetika MeSH
- hypertenze * genetika MeSH
- Liddleův syndrom * genetika MeSH
- lidé MeSH
- nesmyslný kodon * MeSH
- renin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
PURPOSE: Liddle syndrome is a hereditary form of arterial hypertension caused by mutations in the genes coding of the epithelial sodium channel - SCNN1A, SCNN1B and SCNN1G. It is characterised by early onset of hypertension and variable biochemical features such as hypokalaemia and low plasma concentrations of renin and aldosterone. Phenotypic variability is large and, therefore, LS is probably underdiagnosed. Our objective was to examine a family suspected from Liddle syndrome including genetic testing and evaluate clinical and biochemical features of affected family members. MATERIALS AND METHODS: Thirteen probands from the Czech family, related by blood, underwent physical examination, laboratory tests, and genetic testing. Alleles of SCNN1B and SCNN1G genes were examined by PCR amplification and Sanger sequencing of amplicons. RESULTS: We identified a novel mutation in the β-subunit of an epithelial sodium channel coded by the SCNN1B gene, causing the nonsense mutation in the protein sequence p.Tyr604*. This mutation was detected in 7 members of the family. The mutation carriers differed in the severity of hypertension and hypokalaemia which appeared only after diuretics in most of them; low aldosterone level (< 0.12 nmol/l) was, however, present in all. CONCLUSIONS: This finding expands the spectrum of known mutations causing Liddle syndrome. Hypoaldosteronemia was 100% sensitive sign in the mutation carriers. Low levels are observed especially in the Caucasian population reaching 96% sensitivity. Assessment of plasma aldosterone concentration is helpful for differential diagnosis of arterial hypertension. CONDENSED ABSTRACT: Liddle syndrome is a hereditary form of arterial hypertension caused by mutations in the genes encoding the epithelial sodium channel's α-, β- and γ-subunit. It is usually manifested by early onset of hypertension accompanied by low potassium and aldosterone levels. We performed a physical examination, laboratory tests and genetic screening in 13 members of a Czech family. We found a new mutation of the SCNN1B gene which encodes the β-subunit of the epithelial sodium channel. We describe the variability of each family member phenotype and point out the relevance of using aldosterone levels as a high sensitivity marker of Liddle syndrome in Caucasians.
2nd Department of Internal Medicine University Hospital Pilsen Czech Republic
Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Department of Microbiology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Institute of Biology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
- 000
- 00000naa a2200000 a 4500
- 001
- bmc22003540
- 003
- CZ-PrNML
- 005
- 20220127150124.0
- 007
- ta
- 008
- 220113s2021 xxk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1080/08037051.2021.1942785 $2 doi
- 035 __
- $a (PubMed)34223773
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxk
- 100 1_
- $a Mareš, Štěpán $u Second Department of Internal Medicine, University Hospital, Pilsen, Czech Republic $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- 245 12
- $a A novel nonsense mutation in the β-subunit of the epithelial sodium channel causing Liddle syndrome / $c Š. Mareš, J. Filipovský, K. Vlková, M. Pešta, V. Černá, J. Hrabák, J. Mlíková Seidlerová, O. Mayer
- 520 9_
- $a PURPOSE: Liddle syndrome is a hereditary form of arterial hypertension caused by mutations in the genes coding of the epithelial sodium channel - SCNN1A, SCNN1B and SCNN1G. It is characterised by early onset of hypertension and variable biochemical features such as hypokalaemia and low plasma concentrations of renin and aldosterone. Phenotypic variability is large and, therefore, LS is probably underdiagnosed. Our objective was to examine a family suspected from Liddle syndrome including genetic testing and evaluate clinical and biochemical features of affected family members. MATERIALS AND METHODS: Thirteen probands from the Czech family, related by blood, underwent physical examination, laboratory tests, and genetic testing. Alleles of SCNN1B and SCNN1G genes were examined by PCR amplification and Sanger sequencing of amplicons. RESULTS: We identified a novel mutation in the β-subunit of an epithelial sodium channel coded by the SCNN1B gene, causing the nonsense mutation in the protein sequence p.Tyr604*. This mutation was detected in 7 members of the family. The mutation carriers differed in the severity of hypertension and hypokalaemia which appeared only after diuretics in most of them; low aldosterone level (< 0.12 nmol/l) was, however, present in all. CONCLUSIONS: This finding expands the spectrum of known mutations causing Liddle syndrome. Hypoaldosteronemia was 100% sensitive sign in the mutation carriers. Low levels are observed especially in the Caucasian population reaching 96% sensitivity. Assessment of plasma aldosterone concentration is helpful for differential diagnosis of arterial hypertension. CONDENSED ABSTRACT: Liddle syndrome is a hereditary form of arterial hypertension caused by mutations in the genes encoding the epithelial sodium channel's α-, β- and γ-subunit. It is usually manifested by early onset of hypertension accompanied by low potassium and aldosterone levels. We performed a physical examination, laboratory tests and genetic screening in 13 members of a Czech family. We found a new mutation of the SCNN1B gene which encodes the β-subunit of the epithelial sodium channel. We describe the variability of each family member phenotype and point out the relevance of using aldosterone levels as a high sensitivity marker of Liddle syndrome in Caucasians.
- 650 12
- $a nesmyslný kodon $7 D018389
- 650 _2
- $a epiteliální sodíkový kanál $x genetika $7 D053503
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a hypertenze $x genetika $7 D006973
- 650 12
- $a Liddleův syndrom $x genetika $7 D056929
- 650 _2
- $a renin $7 D012083
- 651 _2
- $a Česká republika $7 D018153
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Filipovský, Jan $u Second Department of Internal Medicine, University Hospital, Pilsen, Czech Republic $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- 700 1_
- $a Vlková, Kateřina $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic $u Department of Microbiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- 700 1_
- $a Pešta, Martin $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic $u Institute of Biology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- 700 1_
- $a Černá, Václava $u Institute of Biology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- 700 1_
- $a Hrabák, Jaroslav $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic $u Department of Microbiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- 700 1_
- $a Mlíková Seidlerová, Jitka $u Second Department of Internal Medicine, University Hospital, Pilsen, Czech Republic $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- 700 1_
- $a Mayer, Otto $u Second Department of Internal Medicine, University Hospital, Pilsen, Czech Republic $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- 773 0_
- $w MED00000810 $t Blood pressure $x 1651-1999 $g Roč. 30, č. 5 (2021), s. 291-299
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/34223773 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20220113 $b ABA008
- 991 __
- $a 20220127150120 $b ABA008
- 999 __
- $a ok $b bmc $g 1751102 $s 1154689
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2021 $b 30 $c 5 $d 291-299 $e 20210705 $i 1651-1999 $m Blood pressure $n Blood Press $x MED00000810
- LZP __
- $a Pubmed-20220113