Renal tubulopathies

Gene: WDR72

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 4 Dec 2024, 5:01 p.m. | Last Modified: 4 Dec 2024, 5:01 p.m.

Panel Version: 4.21

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Additional families reported with distal renal tubular acidosis, along with amelogenesis imperfecta.

PMID: 30779877 (Zhang et al 2019) - 6 families (1 African, 5 Turkish) identified using WES with biallelic WDR72 variants. The affected members showed generalized hypomaturation Amelogenesis imperfecta. 2 families, although unrelated, shared the same variant. 3 out of the 8 tested patients showed decreased serum pH, consistent with a diagnosis of renal tubular acidosis.

PMID: 31959358 - (Jobst-Schwan et al 2020) - 2 families (Indian, Turkish) with different homozygous variants in WDR72 identified by WES. All 3 affected individuals had Distal renal tubular acidosis. 1 individual is reported to have nephrocalcinosis.

PMID: 33033857 - Khandelwal et al 2021 - 4 patients, from three unrelated consanguineous families, with RTA and amelogenesis imperfecta. Genome analysis of 3 of the patients identified 3 different homozygous nonsense variants in WDR72. Ultrasound showed bilateral grade I medullary nephrocalcinosis in the 3 patients.

Created: 1 Mar 2023, 9:46 p.m. | Last Modified: 1 Mar 2023, 9:46 p.m.

Panel Version: 3.4

Comment on list classification: Rating this gene as amber as 2 reported families to date.

Created: 12 Feb 2019, 10:38 p.m.

No association with a renal phenotype in OMIM (only with Amelogenesis imperfecta) or Gene2Phenotype.

PMID: 30028003 (Rungroj et al 2018) report 2 families, of Thai and Indian ethnicities, with compound heterozygous and homozygous nonsense WDR72 variations respectively. Both were affected by hereditary distal renal tubular acidosis (dRTA). 3 different variants were found in WDR72; c.1777A>G:p.R593G and c.2522T>A:p.L841Q (predicted as disease causing or damaging, found as compound heterzygotes in family 1) and c.2686C>T:p.R896X. (protein truncating, homozygous in family 2). The truncating variant has been previously reported in a Pakistani family affected by hypomaturation AI, however no other clinical phenotypes in the patients were reported (PMID: 21196691).

Patients in family 1 presented with proximal muscle weakness and/or growth retardation at ages under 7 years. One member of family 1 also had nephrolithiasis and localized enamel hypoplasia. Family 2 has consanguineous parents with one affected child which presented with hypoplastic amelogenesis imperfect in addition to dRTA. She also showed nephrocalcinosis.

Created: 12 Feb 2019, 10:36 p.m. | Last Modified: 1 Mar 2023, 7:39 p.m.

Panel Version: 3.4

Green List (high evidence)

Should be added to gene panel
Sources: Literature

Created: 6 Nov 2018, 8:56 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
distal RTA

Publications

• 30028003