Nephrocalcinosis or nephrolithiasis

Gene: SLC2A9

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

Comment on list classification: Changing rating from red to green. 3 unrelated cases with Hypouricemia, renal, with Nephrolithiasis in some family members.

Created: 30 Oct 2019, 3:02 p.m. | Last Modified: 30 Oct 2019, 3:02 p.m.

Panel Version: 1.33

Comment on mode of inheritance: Both monoallelic and biallelic for Hypouricemia, renal. However, the reported cases with nephrolithiasis are homozygous.

Created: 30 Oct 2019, 2:59 p.m. | Last Modified: 30 Oct 2019, 2:59 p.m.

Panel Version: 1.32

Associated with Hypouricemia, renal, 2 #612076 (AD, AR) in OMIM.

Cases with nepthrolithiasis:
PMID: 19926891 - Dinour et al 2010 - studied two unrelated consanguineous families who had severe hereditary hypouricemia and did not have a URAT1 defect. Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. Nephrolithiasis was seen in some members of both families.

PMID: 21256783 - Stiburkova et al 2011 - proband and her brother from a Czech family with renal hypouricemia have a one nucleotide homozygous insertion in exon 3 in the SLC2A9 gene resulting in a truncated protein (p.Ile118HisfsX27). The brother showed urolithiasis.

Cases with no report of nepthrolithiasis:
PMID: 19026395 - Matsuo et al 2008 - report two loss-of-function heterozygous mutations in GLUT9 (SLC2A9)(R380W and R198C) in renal hypouricemic patients who have no URAT1 mutations but it is not reported whether they have Nephrocalcinosis/nephrolithiasis.

PMID: 21810765 - 2 cases renal hypouricemia and variants in SLC2A9 - no nephrolithiasis reported
PMID: 29486147 - 2 cases with renal hypouricemia and variants in SLC2A9 - no nephrolithiasis reported
PMID: 27116386 - 1 case with renal hypouricemia and variant in SLC2A9 - no nephrolithiasis reported
PMID: 24940677 - 1 case with renal hypouricaemia and variant in SLC2A9 - no mention of nepthrolithiasis

Summary, clear association of variants in SLC2A9 with renal hypouricaemia . 3 cases reported with nepthrolithiasis/urothilthiasis but many more cases where it is not mentioned.

Created: 20 Oct 2019, 9:08 p.m. | Last Modified: 30 Oct 2019, 2:57 p.m.

Panel Version: 1.31

Mode of inheritance submitted by expert was "AD, AR".

Created: 8 Jul 2015, 12:43 p.m.