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| Renal Macrocystic Disease v0.76 | PKHD1 |
Bryony Thompson changed review comment from: Emerging evidence of a monoallelic association with polycystic kidney with/without liver cysts. Enrichment of monoallelic PKHD1 LoF variants (P = 2.98e-08, OR 4.07, 95%CI 2.24-6.88) in 100K GP cystic kidney disease cohort. 50 cases, of which 22 were solved (3 ARPKD & 19 PKD1/2), 2 were partially solved (likely ARPKD), 24 were unsolved (4 with predicted deleterious missense in PKD1/2), and 2 were unascertainable. 18/1209 - with only monoallelic PKHD1 as plausible cause. Enrichment in unexplained (n=266) CyKD cases (P = 5.85e-6, OR 2.92, 95% CI 1.69-4.76). 100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6).; to: Emerging evidence of a monoallelic association with polycystic kidney with/without liver cysts. PMID: 39190485 - Enrichment of monoallelic PKHD1 LoF variants (P = 2.98e-08, OR 4.07, 95%CI 2.24-6.88) in 100K GP cystic kidney disease cohort. 50 cases, of which 22 were solved (3 ARPKD & 19 PKD1/2), 2 were partially solved (likely ARPKD), 24 were unsolved (4 with predicted deleterious missense in PKD1/2), and 2 were unascertainable. 18/1209 - with only monoallelic PKHD1 as plausible cause. Enrichment in unexplained (n=266) CyKD cases (P = 5.85e-6, OR 2.92, 95% CI 1.69-4.76). 100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6). PMID: 21945273 - study suggests carrier status for ARPKD is a predisposition to polycystic liver disease and renal involvement. Ultrasound evaluations on 110 parents from 64 independent ARPKD families (85 molecularly confirmed) identified increased medullary echogenicity in 6 (5.5%) and multiple small liver cysts in 10 parents (9%). Ages of the group ranged from 27 to 66 years (39.5 ± 6.8). |
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| Renal Macrocystic Disease v0.72 | COL4A3 |
Bryony Thompson changed review comment from: PMID: 38514012 - Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5). A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002). PMID: 39190485 - Enrichment of monoallelic COL4A3 rare variants (P = 1.26e-6, OR 3.02, 95% CI 2.10-4.22) in 100K GP cystic kidney disease cohort. Enrichment in “unsolved” (eg removing PKD1 & PKD2 diagnoses), n=308 (P = 6.83e-7, OR 4.93, 95% CI 2.77-8.11). 15/1209 - 9 are Gly-altering in the collagen triple helix domain, 1 stopgain, & 5 missense/inframe indel. 4 of the COL4A3 cases had liver cysts 100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6). Sources: Literature; to: PMID: 38514012 - Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5), mostly ADAS. A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002). The cystic phenotype in the AS patients was associated with an older age and lower eGFR levels. PMID: 39190485 - Enrichment of monoallelic COL4A3 rare variants (P = 1.26e-6, OR 3.02, 95% CI 2.10-4.22) in 100K GP cystic kidney disease cohort. Enrichment in “unsolved” (eg removing PKD1 & PKD2 diagnoses), n=308 (P = 6.83e-7, OR 4.93, 95% CI 2.77-8.11). 15/1209 - 9 are Gly-altering in the collagen triple helix domain, 1 stopgain, & 5 missense/inframe indel. 4 of the COL4A3 cases had liver cysts 100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6). Sources: Literature |
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| Renal Macrocystic Disease v0.71 | COL4A3 |
Bryony Thompson gene: COL4A3 was added gene: COL4A3 was added to Renal Macrocystic Disease. Sources: Literature Mode of inheritance for gene: COL4A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: COL4A3 were set to 39190485; 38514012 Phenotypes for gene: COL4A3 were set to Alport syndrome MONDO:0018965 Review for gene: COL4A3 was set to GREEN gene: COL4A3 was marked as current diagnostic Added comment: PMID: 38514012 - Multiple kidney cysts, usually with normal kidney volume, were found in 37% (26/70) of patients with a genetically confirmed AS (COL4A3-5). A few patients' kidney volumes were similar to autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS compared to those with IgA nephropathy (42% vs 19%; P=0.002). PMID: 39190485 - Enrichment of monoallelic COL4A3 rare variants (P = 1.26e-6, OR 3.02, 95% CI 2.10-4.22) in 100K GP cystic kidney disease cohort. Enrichment in “unsolved” (eg removing PKD1 & PKD2 diagnoses), n=308 (P = 6.83e-7, OR 4.93, 95% CI 2.77-8.11). 15/1209 - 9 are Gly-altering in the collagen triple helix domain, 1 stopgain, & 5 missense/inframe indel. 4 of the COL4A3 cases had liver cysts 100K GP WGS case-control analysis: cystic kidney disease cohort n=1209 vs ancestry-matched controls n=29,096. Gene-based collapsing rare variant association with SAIGE-GENE (P<2.6e-6). Sources: Literature |
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| Renal Macrocystic Disease v0.32 | LRP5 |
Zornitza Stark gene: LRP5 was added gene: LRP5 was added to Renal Macrocystic Disease. Sources: Expert list Mode of inheritance for gene: LRP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LRP5 were set to 25920554; 24706814 Phenotypes for gene: LRP5 were set to Polycystic liver disease 4 with or without kidney cysts, MIM# 617875 Review for gene: LRP5 was set to RED Added comment: 5 families reported. However, some non-penetrance reported in family members in original family. In two of the families reported subsequently, PKD1 LP variants were found and LRP5 variant was postulated to be a modifier. Note that one of the variants p.Arg1036Gln is present in 692 individuals in gnomad, p.Trp560Cys is present in 9, and p.Arg1135Cys is present in 70. Overall limited evidence for association with cystic renal phenotype. Note the gene has a well-established association with eye/bone phenotypes. Sources: Expert list |
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| Renal Macrocystic Disease v0.24 | PKD1 | Zornitza Stark Marked gene: PKD1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.24 | PKD1 | Zornitza Stark Gene: pkd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.24 | PKD1 | Zornitza Stark Phenotypes for gene: PKD1 were changed from to Polycystic kidney disease 1, MIM# 173900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.23 | PKD1 | Zornitza Stark Mode of inheritance for gene: PKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.22 | PKD1 | Chern Lim reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 1, MIM# 173900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Macrocystic Disease v0.0 | PKD1 |
Zornitza Stark gene: PKD1 was added gene: PKD1 was added to Renal cystic disease_KidGen. Sources: KidGen_Cystic v38.1.0,Expert Review Green Mode of inheritance for gene: PKD1 was set to Unknown |
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