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| Proteinuric renal disease v1.218 | PDSS2 |
Eleanor Williams edited their review of gene: PDSS2: Added comment: The gene is associated with Coenzyme Q10 deficiency, primary, 3 (#614652) in OMIM and COENZYME Q10 DEFICIENCY, PRIMARY, 3 (confirmed) in Gene2Phenotype. PMID: 29032433 - Iványi et al 2018 - 1 case - male child of healthy, nonconsanguineous Caucasian parents. At 7 months of age he had general edema, muscle hypotonia, mild inspiratory stridor, and global developmental delay. He did not react to auditory stimuli, and they detected no tracking and focusing eye movements. Urinalysis revealed proteinuria. A heterozygous missense mutation in the PDSS2 gene in exon 3 was found (c.485A > G, p.His162Arg) (maternally inherited) along with a heterozygous 2923-bp deletion that affected a part of exon 8 in the PDSS2 gene. The paternal allele is the NM_020381.3:c.1042_1148-2816del, which causes a 107-base long deletion of exon 8. Despite high-dose CoQ10 treatment he died at 8 months of age. PMID: 25349199 - Sadowski et al 2015 - 2 cases with homozygous missense changes in PDSS2 in patients with Steroid-resistant nephrotic syndrome. They performed exon sequencing of NPHS2 and WT1 for 1783 unrelated, international families with Steroid-resistant nephrotic syndrome (SRNS) and then examined all patients by microfluidic multiplex PCR and next-generation sequencing for all 27 genes known to cause SRNS if mutated. 2 families were molecularly diagnosed with a causative variant in PDSS2 by multiplex PCR (c.1145C>T,p.Ser382Leu and c.1151C>A, p.Ala384Asp). PMID: 23926186 - Gasser et al 2013 - genotyped 377 patients with primary Focal segmental glomerulosclerosis (FSGS) or collapsing glomerulopathy, together with 900 controls, for 9 single-nucleotide polymorphisms in the PDSS2 gene in a case-control study. The nine selected SNPs were distributed at approximately equal distances across the PDSS2 gene. All the SNPs that were genotyped occurred within noncoding regions of the gene. They demonstrated that homozygous genotypes for variant alleles for the PDSS2 gene were more common in FSGS patients than controls and that a single haplotype containing three of these SNPs was more common in European American, but not African American, FSGS patients, suggesting that PDSS2 may be an FSGS susceptibility gene. PMID:17186472 - Lopez et al 2006 - 1 family with child who presented with neonatal pneumonia and hypotonia, developed refractory left-sided seizures with secondary generalization, and became progressively floppy. At age 7 mo, severe episodic vomiting prompted duodenal tube feeding, and was diagnosed with nephrotic syndrome due to low serum albumin and massive proteinuria. They found two nonsynonymous nucleotide changes in PDSS2, each inherited from one parent. Functional tests on cultured patient fibroblast indicate that endogenous levels of decaprenyl diphosphate are reduced. Mouse model: PMID: 18437205 - Peng et al 2008 - Kidney disease in mice with missense Pdss2(kd/kd) genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2(kd/kd) mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2(loxP/loxP) knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Summary: 4 cases of children with nephrotic syndrome and homozygous or compound heterozygous variants in PDSS2. In two cases the variants are reported to segregate with the disease in the family. Additional evidence from a case control study that PDSS2 is a FSGS susceptibility gene and from a mouse Pdss2 knockout model.; Changed publications: PMID: 23926186 |
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| Proteinuric renal disease v1.129 | WT1 | Eleanor Williams Phenotypes for gene: WT1 were changed from to Denys-Drash syndrome #194080; Frasier syndrome #136680; Wilms tumor, type 1 #194070 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proteinuric renal disease v1.128 | WT1 | Eleanor Williams Publications for gene: WT1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proteinuric renal disease v1.16 | WT1 | Eleanor Williams reviewed gene: WT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Denys-Drash syndrome #194080, Frasier syndrome #136680, Wilms tumor, type 1 #194070; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proteinuric renal disease v1.15 | WT1 |
Eleanor Williams Source NHS GMS was added to WT1. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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