Molecular Analysis of the Carboxy Terminus of the Beta and Gamma Subunits of the Epithelial Sodium Channel in Patients with End-Stage Renal Disease

Födinger, Manuela; Schedler, Dagmar; Fritsche-Polanz, Robert; Hörl, WalterH.; Sunder‐Plassmann, Gere

doi:10.1159/000045320

Cited by 7 publications

(2 citation statements)

References 40 publications

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“…Several previous studies examined partial sequences of ␤and ␥subunits (only selected exons in the carboxyl-terminal region) (35)(36)(37) in hypertensive subjects. Although Persu et al (35) identified novel rare SNPs, no mutation was found to be definitively associated with hypertension (35)(36)(37). Exons 8 and 12, noted in a previous study (35), are here numbered 9 and 13, as we now know that there are 13 exons in the ␤ ENaC gene (9), not 12.…”

Section: Sequence Variants In Genes Encoding Enac Subunitsmentioning

confidence: 99%

Novel Mutations Responsible for Autosomal Recessive Multisystem Pseudohypoaldosteronism and Sequence Variants in Epithelial Sodium Channel α-, β-, and γ-Subunit Genes

Saxena

Hanukoglu

Saxena

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

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Multisystem pseudohypoaldosteronism (PHA), is a syndrome of unresponsiveness to aldosterone with autosomal recessive inheritance. Previously we showed that mutations in the epithelial sodium channel (ENaC) alpha-, beta-, and gamma-subunits are responsible for PHA. In this study we examined four independent probands with multisystem PHA, three of whom were born to consanguineous parents. In our search for mutations we also determined the complete coding sequences of each of the three genes encoding alpha-, beta-, and gamma-subunits in individuals representing different ethnic groups. Our analyses revealed the following homozygous mutations in three probands: 1) insertion of a T in exon 8 of the alpha ENaC gene that causes a frameshift error at Tyr(447) and leads to a premature stop codon at K459 in a Pakistani patient; 2) R508stop mutation in exon 11 of the alpha ENaC gene in an Indian patient; and 3) a splice site mutation in intron 12 of the beta ENaC gene (1669 + 1 g-->a) in a Scottish patient. The parents were heterozygous for the latter two mutations. The second mutation was previously observed in an Iranian Jewish patient. Our sequencing of the alpha-, beta-, and gamma-coding sequences revealed some sequence variants, some of which may represent single nucleotide polymorphisms. The gamma-subunit protein sequence was completely conserved in the six subjects examined. The homozygous mutations identified in the alpha and beta ENaC genes should result in reduced or abolished ENaC activity in PHA patients, explaining the disease symptoms.

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Section: Sequence Variants In Genes Encoding Enac Subunitsmentioning

confidence: 99%

Novel Mutations Responsible for Autosomal Recessive Multisystem Pseudohypoaldosteronism and Sequence Variants in Epithelial Sodium Channel α-, β-, and γ-Subunit Genes

Saxena

Hanukoglu

Saxena

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

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“…Thus, mutations in these genes may not be associated with the disease [46]. One has to take into consideration, however, that the search was often restricted to the cytoplasmic carboxy-terminal domain of the SCNN1 genes.…”

Section: The Epithelial Sodium Channel and Its Implication In Essentimentioning

confidence: 99%

Epithelial sodium channel, salt intake, and hypertension

Hummler

2003

Current Science Inc

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The epithelial sodium channel (ENaC) is a membrane protein made of three different but homologous subunits (a, b, and g) present in the apical membrane of epithelial cells of, for example, the distal nephron. This channel is responsible for salt reabsorption in the kidney and can cause human diseases by increasing channel function in Liddle's syndrome, a form of hereditary hypertension, or by decreasing channel function in pseudohypoaldosteronism type I, a salt-wasting disease in infancy. This review briefly discusses recent advances in understanding the implication of ENaC in Liddle's syndrome and in pseudohypoaldosteronism type I, both caused by mutations in the SCNN1 (ENaC) genes. Furthermore, it is still an open question to which extent SCNN1 genes coding for ENaC might be implicated in essential hypertension. The development of Scnn1 genetically engineered mouse models will provide the opportunity to test the effect of environmental factors, like salt intake, on the development of this kind of salt- sensitive hypertension.

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Sporadic cases of Liddle's syndrome: Clues to essential hypertension?

Alper

2001

American Journal of Kidney Diseases

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Molecular Analysis of the Carboxy Terminus of the Beta and Gamma Subunits of the Epithelial Sodium Channel in Patients with End-Stage Renal Disease

Cited by 7 publications

References 40 publications

Novel Mutations Responsible for Autosomal Recessive Multisystem Pseudohypoaldosteronism and Sequence Variants in Epithelial Sodium Channel α-, β-, and γ-Subunit Genes

Novel Mutations Responsible for Autosomal Recessive Multisystem Pseudohypoaldosteronism and Sequence Variants in Epithelial Sodium Channel α-, β-, and γ-Subunit Genes

Epithelial sodium channel, salt intake, and hypertension

Sporadic cases of Liddle's syndrome: Clues to essential hypertension?

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