Proteinuric renal disease

Gene: PRDM15

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 4 Dec 2024, 1:52 p.m. | Last Modified: 4 Dec 2024, 1:52 p.m.

Panel Version: 4.22

Comment on list classification: There is sufficient evidence available (six unrelated individuals with three different biallelic variants, mouse and Xenopus models and functional data) for the promotion of this gene to green rating in the next GMS update.

Created: 12 Apr 2024, 8:57 a.m. | Last Modified: 12 Apr 2024, 8:57 a.m.

Panel Version: 4.10

Four unrelated individuals of Arab descent were reported with a Galloway-Mowat syndrome (GAMOS)-like syndrome, including microcephaly, abnormal cerebral gyration, developmental delay, and heavy proteinuria. In addition to glomerular proteinuria, all four individuals were noted to have tubular involvement, suggesting a more generalised renal developmental abnormality. All these patients had the same homozygous variant (p.Cys844Tyr).

The querying of whole-exome sequencing data from approximately 1000 individuals with steroid-resistant nephrotic syndrome identified two different homozygous missense variants in PRDM15 (p.Met154Lys and p.Glu190Lys) in two individuals from unrelated families with early-onset nephrotic syndrome and in whom no other genetic causes of nephrotic syndrome were identified.

PRDM15 knockdown in Xenopus embryos disrupted pronephric development and human wild-type PRDM15 RNA rescued the disruption, but the three PRDM15 variants did not. In addition, CRISPR-mediated knockout of PRDM15 in human podocytes led to dysregulation of several renal developmental genes.

This gene has been associated with PRDM15-related renal and neurodevelopmental disorder in the DD panel in Gene2Phenotype database (with 'limited' rating), but has not yet been associated with any relevant phenotypes in OMIM.

Created: 12 Apr 2024, 8:55 a.m. | Last Modified: 12 Apr 2024, 8:55 a.m.

Panel Version: 4.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
steroid-resistant nephrotic syndrome, MONDO:0044765

Publications

• 33593823

I don't know

Four consanguineous families reported with same homozygous variant, C844Y, shown to be LoF. Syndromic SRNS including HPE, brain malformations, polydactyly, congenital heart disease. Mouse model, extensive functional data focused on the brain phenotype. Two additional homozygous missense identified with isolated SRNS.
Sources: Literature

Created: 10 May 2021, 10:04 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Steroid resistant nephrotic syndrome; Holoprosencephaly

Publications

• 31950080