Nephrocalcinosis or nephrolithiasis

Gene: SLC22A12

Green List (high evidence)

Can be associated with urate stones.

Created: 30 Oct 2019, 11:59 a.m. | Last Modified: 30 Oct 2019, 11:59 a.m.

Panel Version: 1.23

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on list classification: Promoting from red to green. Sufficient number of cases with biallelic or compound heterozygous variants in this gene and a relevant phenotype reported. A few heterozygous cases also reported but the evidence is not so strong (asymptomatic family members with the same variant, only the SLC22A12 gene looked at).

Created: 30 Oct 2019, 2:50 p.m. | Last Modified: 30 Oct 2019, 2:50 p.m.

Panel Version: 1.31

Comment on mode of inheritance: The evidence for biallelic inheritance is stronger so setting to this for now. AR in OMIM.

Created: 30 Oct 2019, 2:34 p.m. | Last Modified: 30 Oct 2019, 3:17 p.m.

Panel Version: 1.35

Associated with Hypouricemia, renal #220150 (AR) in OMIM with Uric acid nephrolithiasis listed as a clinical feature.

PMID: 29486147 - Claverie-Martin et al 2018 - report patients from 6 unrelated Spanish families with Renal hypouricemia and variants in SLC22A12. Nephrolithiasis was reported in one Roma patient with compound heterozygous variants in this gene (L415_G417del, T467M).

PMID: 29958533 - Vidanapathirana et al 2018 - report a 9 year old Sri Lankan boy with renal hypouricemia who presented with nephrolithiasis and haematuria. He was found to have a potentially deleterious missense variant c.1400C > T (p.T467 M, rs200104135) in heterozygous state. This variant has been previously identified in homozygous and/or compound heterozygous state with other causative SLC22A12 variant c.1245_1253del (p.L415_G417del) in Roma population. The genotype c.[1400C > T] was found in the proband, his sister and father (both asymptomatic).

PMID: 18492088 - Ichida et al 2008 - identified SLC22A12 mutations in 66 of 71 Japanese patients with hypouricemia. A total of 13 mutations, including 3 novel mutations, were identified. Urolithiasis occurred in 5 of the patients with variants in SLC22A12. 4 were homozygous or compound heterozygous, one was heterozygous. One variant G774A/W258X was the most common variant and is thought to be a founder mutation.

PMID: 15912381 - Cheong et al 2005 - studied the SLC22A12 gene in five Korean patients with idiopathic renal hypouricemia, 1 patient with a R90H substitution had uric acid urolithiasis. The variant was heterozygous.

Created: 20 Oct 2019, 3:08 p.m. | Last Modified: 30 Oct 2019, 2:42 p.m.

Panel Version: 1.29

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• 29486147
• 29958533
• 18492088
• 15912381