Skeletal dysplasia

Gene: SCNN1G

Green List (high evidence)

Variants resulting in constitutive activation of epithelial sodium channel activity have been demonstrated in the beta and gamma subunits as the cause of the autosomal dominant form of hypertension, Liddle syndrome, which is characterized by volume expansion, hypokalemia, and alkalosis.

Variants causing loss of epithelial sodium channel activity cause the converse phenotype of volume depletion, hyperkalaemia and acidosis characteristic of patients with pseudohypoaldosteronism type I.

Well established gene-disease associations.

Created: 19 Jul 2021, 3:23 a.m. | Last Modified: 19 Jul 2021, 3:23 a.m.

Panel Version: 0.8428

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Liddle syndrome 2, MIM# 618114; Pseudohypoaldosteronism, type I, MIM# 264350

I don't know

Encodes for the gamma subunit of the epithelial sodium channel, which is distributed along the motile cilia. (PMID: 22207244). Respiratory problems is a feature of pseudohypoaldosteronism Type I. Minimal reports to date.

Kozina 2019; PMID: 31655555: Reported one family and reviewed 6 other families with het truncating variants in SCNN1G causing Liddle syndrome. Unsure if features resemble ciliopathies

Bush 2019; PMID: 30801930; ENaC mutations, especially in-trans with a CFTR mutation, are thought to be risk factors for bronchiectasis, rather than actually causative

Nur 2017; PMID: 28484659; Review of PHA1. 2 patients reported with biallelic LoF type variants in SCNN1G.
Sources: Expert Review

Created: 6 May 2020, 1:59 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Bronchiectasis with or without elevated sweat chloride 3 (MIM#613071); Liddle syndrome 2 (MIM#618114); Pseudohypoaldosteronism, type I (MIM#264350)

Publications

• 22207244
• 31655555
• 30801930
• 28484659