Renal tubulopathies

Gene: SLC5A2

Comment on list classification: Changed rating to Amber to reflect NHS signed-off rating, will be examined at next panel review.

Created: 16 Oct 2020, 8:25 a.m. | Last Modified: 16 Oct 2020, 8:25 a.m.

Panel Version: 2.18

Green List (high evidence)

Comment on list classification: Reverting this gene to green. It was green at the initial sign off (v2.3 in Feb 2020) and was reverted to amber in error in October 2020 before re-sign off.

Created: 19 Jan 2021, 2:40 p.m. | Last Modified: 19 Jan 2021, 2:40 p.m.

Panel Version: 2.25

Comment on list classification: Changing rating from red to green as >3 cases reported.

Created: 5 Sep 2019, 9:55 p.m. | Last Modified: 5 Sep 2019, 9:55 p.m.

Panel Version: 1.172

Associated with Renal glucosuria #233100 (both AD and AR) in OMIM.

PubMed: 12436245 - van den Heuvel et al. (2002) - 1 case. Turkish patient with congenital isolated renal glucosuria and a homozygous nonsense mutation in exon 11 leading to the formation of a truncated cotransporter. Both parents and a younger brother, all 3 without renal glucosuria, were heterozygous for the mutation.

PubMed: 21165652 - Yu et al. 2011 - screened the SGLT2 (now known as SLC5A2) gene in 4 patients in 4 unrelated Chinese families had persistent glucosuria with no polyuria/polydipsia, and no history of other renal diseases. They identified 5 novel mutations in the probands, including three missense mutations and two splice mutations. All four probands were heterozygous or compound heterozygous for SGLT2 mutations and none of the five identified mutations was detected in 110 chromosomes derived from 55 healthy, unrelated individuals, indicating that these mutations do not represent common polymorphisms. Compound heterozygous patients had more significant glucosuria. Functional studies also carried out.

PubMed: 26376857- Dhayat et al 2016 - report a Swiss family with SLC16A12-associated cataract and microcornea, in which 5 affected individuals also exhibited renal leak glucosuria, They identified an additional heterozygous missense mutation in the SLC5A2 gene that segregated fully with renal leak glucosuria in the family.

Created: 2 Sep 2019, 9:36 p.m. | Last Modified: 2 Sep 2019, 9:36 p.m.

Panel Version: 1.82

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: SLC5A2; 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
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Renal glucosuria, MIM 233100

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