Nephrocalcinosis or nephrolithiasis

Gene: SLC34A3

The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 30 Jan 2023, 2:21 p.m. | Last Modified: 30 Jan 2023, 2:21 p.m.

Panel Version: 3.4

Comment on mode of inheritance: Leaving MOI as Biallelic for now but with recommendation for change to BOTH mono and bi-allelic at the next GMS review.

Created: 2 Aug 2022, 11:12 p.m. | Last Modified: 2 Aug 2022, 11:12 p.m.

Panel Version: 2.33

Green List (high evidence)

Previous review listed as causative only with balletic variants. However numerous reports now show that most (not all) carriers of heterozygous variants also have hypercalciuria, nephrocalcinosis and increased risk of stones, albeit much lower than with balletic variants. An investigation in a cohort of patients with variants in SLC34A3 (PMID: 24700880) showed that the risk of nephrocalcinosis/nephrolithiasis was 46%, 16% and 6% in subjects with biallelic, monoallelic or no causative variants, respectively. Thus, in subjects with nephrocalcinosis, monoallelic variants should be considered causative.

Created: 21 Jul 2022, 11:05 a.m. | Last Modified: 21 Jul 2022, 11:05 a.m.

Panel Version: 2.32

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
hypercalciuria; nephrocalcinosis, nephrolithiasis; hypophosphataemia

Publications

• PMID: 16358214
• 27939817
• 24700880
• 17968493

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HHRH; recent publication added nephrolithiasis.

Publications

• 25296721

Comment on mode of inheritance: PMID: 24700880: evidence that heterozygotes may also have an increased risk of renal calcifications compared to the general public?

Created: 20 May 2016, 8:33 a.m.

Comment on list classification: Originally an amber gene. Promoted after expert review. Multiple examples in OMIM for association with hypophosphatemic rickets with hypercalciuria, hereditary, and a more recent cases for an association with nephrolithiasis, hereditary hypophosphatemia, and hypercalciuria.

Created: 9 May 2016, 1:59 p.m.

Comment on mode of inheritance: Confirmed in expert review and on OMIM.

Created: 9 May 2016, 1:46 p.m.

Mode of inheritance submitted from expert was AR (autosomal recessive).

Created: 8 Jul 2015, 12:53 p.m.