Proteinuric renal disease

Gene: YRDC

I don't know

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

Created: 7 Mar 2022, 11:37 p.m. | Last Modified: 7 Mar 2022, 11:37 p.m.

Panel Version: 2.66

Comment on list classification: Promoting from grey to amber, based on 2 cases plus some functional data. At the next GMS review it could be considered for green rating based on the external expert review.

Created: 16 Jan 2021, 1:10 p.m. | Last Modified: 16 Jan 2021, 1:10 p.m.

Panel Version: 2.44

As expert reviewer notes, Arrondel et al 2019 (PMID:31481669) reports 3 children with Galloway-Mowat syndrome from 2 families of European ancestry. Using WES variants in YRDC were identified; in one family compound het variants (one missense, and one frameshift deletion leading to a stop codon) and in the other family a homozygous in frame deletion. In both families it was found that affected children showed the presence of YRDC transcripts and proteins in cells. Early-onset proteinuria was observed in all affected children. In addition to developmental delay, primary microcephaly was present in the two affected children of one family, and post-natal microcephaly in the other. Using yeast assays to express the human variants, they examined whether human YRDC cDNAs encoding wild-type and mutant proteins could rescue the sua5 deletion (YRDC ortholog) strain which showed a slow growth phentoype. The wild type and p.Ala84Val and p.Leu265del mutants could rescue the phenotype but the p.Val241Ilefs*72 mutant was unable to improve the growth. Patient fibroblasts show lower t6A levels than wildtype.

Created: 16 Jan 2021, 1:05 p.m. | Last Modified: 16 Jan 2021, 1:05 p.m.

Panel Version: 2.43

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Galloway-Mowat syndrome MONDO:0009627

Publications

• 31481669

Green List (high evidence)

Three individuals from two unrelated families with typical features of Galloway-Mowat syndrome including proteinuria, microcephaly, developmental delay and brain malformations. Supportive functional data.
Sources: Literature

Created: 7 Sep 2020, 10:09 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Galloway-Mowat syndrome

Publications

• 31481669

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