Renal tubulopathies

Gene: NR3C2

Green List (high evidence)

Comment on list classification: Changing rating from red to green as more than 3 cases have been reported.

Created: 5 Sep 2019, 4:25 p.m. | Last Modified: 5 Sep 2019, 4:25 p.m.

Panel Version: 1.139

Comment on mode of inheritance: Only one report of biallelic mutations, and in that case there were 3 in the patient, and were reported to occur in healthy populations

Created: 5 Sep 2019, 4:24 p.m. | Last Modified: 5 Sep 2019, 4:24 p.m.

Panel Version: 1.138

Associated with Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy #605115 and Pseudohypoaldosteronism type I, autosomal dominant #177735 in OMIM.

The gene is also known as MCR.

Many cases of Pseudohypoaldosteronism associated with variants in NR3C2 reported in OMIM.

No inheritance pattern listed in OMIM. However, most reports are for monoallelic inheritance (PMID: 9662404, 12788847, 16972228, 16954160). The only report of a biallelic case (PMID: 12483305 Arai et al 2003) was found in In a Japanese patient with sporadic PHA. 3 homozygous substitutions were found that had previously been reported to occur in healthy populations. The authors suggested that 2 or more 'functional' polymorphisms, any of which exhibits only slight effects on function alone and is incapable of causing PHA, may in the right allelic combination induce the negative salt conservation characteristic of PHA.

Created: 31 Aug 2019, 5:27 p.m. | Last Modified: 5 Sep 2019, 4:23 p.m.

Panel Version: 1.136

This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group; Gene Symbol submitted: NR3C2; Suggested initial gene rating: green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided

Created: 3 Feb 2019, 11:32 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pseudohypoaldosteronism type I, autosomal dominant, MIM 177735; Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy MIM 605115 no inheritance pattern

Variants in this GENE are reported as part of current diagnostic practice