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Proteinuric renal disease v1.140 ARHGDIA Eleanor Williams Phenotypes for gene: ARHGDIA were changed from to Nephrotic syndrome, type 8 #615224
Proteinuric renal disease v1.139 ARHGDIA Eleanor Williams Publications for gene: ARHGDIA were set to
Proteinuric renal disease v1.35 ARHGDIA Eleanor Williams commented on gene: ARHGDIA: Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that although it is clearly rare with no variants found in >600 cases in Bristol, it is appropriate for inclusion in the panel.
Proteinuric renal disease v1.16 ARHGDIA Eleanor Williams edited their review of gene: ARHGDIA: Added comment: PMID: 23434736 - Gupta et al 2013 - 2 sisters with congenital nephrotic syndrome who were born to consanguineous parents of Pakistani origin. Using whole exome sequencing, they found both girls have a homozygous in-frame deletion in ARHGDIA, c.553_555del(p.Asp185del). The healthy mother was found to be a heterozygous carrier for this deletion. The father's DNA was unavailable for analysis. Functional studies showed that RhoGDIα protein was strongly expressed in the glomerulus of the adult mouse kidney and that normal binding of mutant protein was impaired.

PMID: 23867502 - Gee et al 2013 - performed homozygosity mapping and then whole exome resequencing in a family of Ashkenazi Jewish origin in whom 2 siblings had early-onset SRNS with renal histology of diffuse mesangial sclerosis. They found in both siblings a homozygous missense mutation (c.518G>T;p.G173V) of ARHGDIA. They then examined 65 additional individuals with DMS and 350 individuals with SRNS, we detected a homozygous mutation (c.358C>T;p.R120X) in an infant (Moroccan) with congenital NS. Functional studies showed both mutant protein had abrogated interaction with RHO GTPases and the nephrotic phenotype was recapitulated in arhgdia-deficient zebrafish.

PMID: 30295827 - Schapiro et al 2019 - screen for 11 AS, aHUS and thrombotic thrombocytopenic purpura-causing genes by exon sequencing and 23 SRNS-causing genes by WES or high-throughput exon sequencing in an international cohort of 371 patients from 362 families presenting with both proteinuria and hematuria before age 25 years. This screen included ARHGDIA. 1 consangineious Jewish family with 2 individuals are homozgous for c.518G>T, p.Gly173Val.

Summary - 4 families with 3 different variants reported. The two Jewish families have the same variant. Functional evidence that the protein is expressed in the kidney and that the function of mutant protein is impared.; Changed publications: 23434736, 23867502, 30295827
Proteinuric renal disease v1.16 ARHGDIA Eleanor Williams reviewed gene: ARHGDIA: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 23434736, PMID: 23867502, PMID: 30295827; Phenotypes: Nephrotic syndrome, type 8 #615224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.15 ARHGDIA Eleanor Williams Source NHS GMS was added to ARHGDIA.
Rating Changed from Green List (high evidence) to Green List (high evidence)