Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
13 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v1.27 | APOA4 |
Ida Ertmanska changed review comment from: PMID: 38096951 Kmochova et al., 2024 3 distantly related families with (NM_000482.4):c.196C>G, p.Leu66Val, 2 distantly related families with c.97G>A, p.Asp33Asn. Method: WGS. Affected individuals presented with chronic kidney disease, with mean age of kidney failure of 64.5 years. Kidney biopsies from affected individuals showed amyloid deposits in the medulla, with Apoa4 protein being the main constituent. p.Leu66Val - 3 heterozygotes in gnomAD v4.1.0 (European), Revel score = 0.27 p.Asp33Asn - not in gnomAD v4, though p.Asp33Glu and p.Asp33Val have been reported; Revel score = 0.31 PMID: 33751222 Murakami et al., 2021 Report of a 68 yo Japanese man, with 4 variants in APOA4: 2 synonymous (p.Thr29Thr, p.Leu128Leu); '6981A>C',p.Asn248Thr; and c.743A>C, p.Asn248Thr - not in gnomAD v4. Only APOA4 was sequenced. Patient had history of renal cysts, diagnosed with HCM 2 years prior. Authors highlight that Apoa4 protein aggregation is causal, but the gene variant may not be. PMID: 27262366 Dasari et al. 2016 Reported 11 patients with Apolipoprotein A-IV associated amyloidosis (mean age at diagnosis 63.5yrs). Biopsies showed large amounts of eosinophilic Congo–red positive amyloid deposits restricted to the renal medulla. ApoA-IV protein was the most abundant peptide in the amyloid deposits. However, molecular analysis was performed in only 2/11 patients, and no APOA4 mutations were found. PMID: 21900878 Sethi et al., 2012 52yo man with CKD and amyloid deposits in the medulla, harbouring 3 common, likely benign APOA4 variants: c.548G>A, p.(Thr29Thr); c.1678G>A, p.(Ser147Asn); c.2378G>T, p.(Gln380His). He also carried 2 APOA1 variants: c.60T>C, p.(His20His) - synonymous, not in gnomAD; c.209T>C, p.(Leu70Pro) - missense, not in gnomAD v4. APOA1 more likely to be causal? Only sequenced these 2 genes. Conflicting functional evidence: PMID: 39699959 Nakamura et al., 2024: TFEB downregulation in aged mice leads to APOA4 amyloidosis, though only 26.7% of mice showed 'extensive' amyloid deposition. Variants in other genes may cause APOA4 to aggregate? APOA4 is linked to Tubulointerstitial kidney disease, autosomal dominant 6, MIM: 621106 (OMIM accessed 18th Dec 2025). Sources: Literature; to: PMID: 38096951 Kmochova et al., 2024 3 distantly related families with (NM_000482.4):c.196C>G, p.Leu66Val, 2 distantly related families with c.97G>A, p.Asp33Asn. Method: WGS. Affected individuals presented with chronic kidney disease, with mean age of kidney failure of 64.5 years. Kidney biopsies from affected individuals showed amyloid deposits in the medulla, with Apoa4 protein being the main constituent. p.Leu66Val - 3 heterozygotes in gnomAD v4.1.0 (European), Revel score = 0.27 p.Asp33Asn - not in gnomAD v4, though p.Asp33Glu and p.Asp33Val have been reported; Revel score = 0.31 PMID: 33751222 Murakami et al., 2021 Report of a 68 yo Japanese man, with 4 variants in APOA4: 2 synonymous (p.Thr29Thr, p.Leu128Leu); '6981A>C',p.Asn248Thr; and c.743A>C, p.Asn248Thr - not in gnomAD v4. Only APOA4 was sequenced. Patient had history of renal cysts, diagnosed with HCM 2 years prior. Authors highlight that Apoa4 protein aggregation is causal, but the gene variant may not be. PMID: 28449784 Bois et al., 2017 13 patients with AApoAIV cardiac amyloidosis, mean age 75 years. Patients had cardiac dysfunction. Of 9 patients evaluated in detail, 8/9 had chronic kidney disease (various stages). Autopsy of 4 cases showed small vessel involvement and prominent medullary renal deposits Genetic analysis was performed, but 'did not identify definitive pathological mutations.' PMID: 27262366 Dasari et al. 2016 Reported 11 patients with Apolipoprotein A-IV associated amyloidosis (mean age at diagnosis 63.5yrs). Biopsies showed large amounts of eosinophilic Congo–red positive amyloid deposits restricted to the renal medulla. ApoA-IV protein was the most abundant peptide in the amyloid deposits. However, molecular analysis was performed in only 2/11 patients, and no APOA4 mutations were found. PMID: 21900878 Sethi et al., 2012 52yo man with CKD and amyloid deposits in the medulla, harbouring 3 common, likely benign APOA4 variants: c.548G>A, p.(Thr29Thr); c.1678G>A, p.(Ser147Asn); c.2378G>T, p.(Gln380His). He also carried 2 APOA1 variants: c.60T>C, p.(His20His) - synonymous, not in gnomAD; c.209T>C, p.(Leu70Pro) - missense, not in gnomAD v4. APOA1 more likely to be causal? Only sequenced these 2 genes. Conflicting functional evidence: PMID: 39699959 Nakamura et al., 2024: TFEB downregulation in aged mice leads to APOA4 amyloidosis, though only 26.7% of mice showed 'extensive' amyloid deposition. Variants in other genes may cause APOA4 to aggregate? APOA4 is linked to Tubulointerstitial kidney disease, autosomal dominant 6, MIM: 621106 (OMIM accessed 18th Dec 2025). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v1.27 | APOA4 |
Ida Ertmanska changed review comment from: PMID: 38096951 Kmochova et al., 2024 3 distantly related families with (NM_000482.4):c.196C>G, p.Leu66Val, 2 distantly related families with c.97G>A, p.Asp33Asn. Method: WGS. Affected individuals presented with chronic kidney disease, with mean age of kidney failure of 64.5 years. Kidney biopsies from affected individuals showed amyloid deposits in the medulla, with Apoa4 protein being the main constituent. p.Leu66Val - 3 heterozygotes in gnomAD v4.1.0 (European), Revel score = 0.27 p.Asp33Asn - not in gnomAD v4, though p.Asp33Glu and p.Asp33Val have been reported; Revel score = 0.31 PMID: 33751222 Murakami et al., 2021 Report of a 68 yo Japanese man, with 4 variants in APOA4: 2 synonymous (p.Thr29Thr, p.Leu128Leu); '6981A>C',p.Asn248Thr; and c.743A>C, p.Asn248Thr - not in gnomAD v4. Only APOA4 was sequenced. Patient had history of renal cysts, diagnosed with HCM 2 years prior. Authors highlight that Apoa4 protein aggregation is causal, but the gene variant may not be. PMID: 27262366 Dasari et al. 2016 Reported 11 patients with Apolipoprotein A-IV associated amyloidosis (mean age at diagnosis 63.5yrs). Biopsies showed large amounts of eosinophilic Congo–red positive amyloid deposits restricted to the renal medulla. ApoA-IV protein was the most abundant peptide in the amyloid deposits. However, molecular analysis was performed in only 2/11 patients, and no APOA4 mutations were found. PMID: 21900878 Sethi et al., 2012 52yo man with CKD and amyloid deposits in the medulla, harbouring 3 common, likely benign APOA4 variants: c.548G>A, p.(Thr29Thr); c.1678G>A, p.(Ser147Asn); c.2378G>T, p.(Gln380His). He also carried 2 APOA1 variants: c.60T>C, p.(His20His) - synonymous, not in gnomAD; c.209T>C, p.(Leu70Pro) - missense, not in gnomAD v4. APOA1 more likely to be causal? Only sequenced these 2 genes. Conflicting functional evidence: PMID: 39699959 Nakamura et al., 2024: TFEB downregulation in aged mice leads to APOA4 amyloidosis - variants in other genes may cause APOA4 to aggregate. APOA4 is linked to Tubulointerstitial kidney disease, autosomal dominant 6, MIM: 621106 (OMIM accessed 18th Dec 2025). Sources: Literature; to: PMID: 38096951 Kmochova et al., 2024 3 distantly related families with (NM_000482.4):c.196C>G, p.Leu66Val, 2 distantly related families with c.97G>A, p.Asp33Asn. Method: WGS. Affected individuals presented with chronic kidney disease, with mean age of kidney failure of 64.5 years. Kidney biopsies from affected individuals showed amyloid deposits in the medulla, with Apoa4 protein being the main constituent. p.Leu66Val - 3 heterozygotes in gnomAD v4.1.0 (European), Revel score = 0.27 p.Asp33Asn - not in gnomAD v4, though p.Asp33Glu and p.Asp33Val have been reported; Revel score = 0.31 PMID: 33751222 Murakami et al., 2021 Report of a 68 yo Japanese man, with 4 variants in APOA4: 2 synonymous (p.Thr29Thr, p.Leu128Leu); '6981A>C',p.Asn248Thr; and c.743A>C, p.Asn248Thr - not in gnomAD v4. Only APOA4 was sequenced. Patient had history of renal cysts, diagnosed with HCM 2 years prior. Authors highlight that Apoa4 protein aggregation is causal, but the gene variant may not be. PMID: 27262366 Dasari et al. 2016 Reported 11 patients with Apolipoprotein A-IV associated amyloidosis (mean age at diagnosis 63.5yrs). Biopsies showed large amounts of eosinophilic Congo–red positive amyloid deposits restricted to the renal medulla. ApoA-IV protein was the most abundant peptide in the amyloid deposits. However, molecular analysis was performed in only 2/11 patients, and no APOA4 mutations were found. PMID: 21900878 Sethi et al., 2012 52yo man with CKD and amyloid deposits in the medulla, harbouring 3 common, likely benign APOA4 variants: c.548G>A, p.(Thr29Thr); c.1678G>A, p.(Ser147Asn); c.2378G>T, p.(Gln380His). He also carried 2 APOA1 variants: c.60T>C, p.(His20His) - synonymous, not in gnomAD; c.209T>C, p.(Leu70Pro) - missense, not in gnomAD v4. APOA1 more likely to be causal? Only sequenced these 2 genes. Conflicting functional evidence: PMID: 39699959 Nakamura et al., 2024: TFEB downregulation in aged mice leads to APOA4 amyloidosis, though only 26.7% of mice showed 'extensive' amyloid deposition. Variants in other genes may cause APOA4 to aggregate? APOA4 is linked to Tubulointerstitial kidney disease, autosomal dominant 6, MIM: 621106 (OMIM accessed 18th Dec 2025). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v1.26 | APOA4 |
Ida Ertmanska gene: APOA4 was added gene: APOA4 was added to Hereditary systemic amyloidosis. Sources: Literature Q4_25_promote_green tags were added to gene: APOA4. Mode of inheritance for gene: APOA4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: APOA4 were set to 21900878; 27262366; 33751222; 38096951; 39699959 Phenotypes for gene: APOA4 were set to Tubulointerstitial kidney disease, autosomal dominant 6, OMIM: 621106; tubulointerstitial kidney disease, autosomal dominant 6, MONDO:0976234; AApoAIV amyloidosis, MONDO:0018589 Review for gene: APOA4 was set to GREEN Added comment: PMID: 38096951 Kmochova et al., 2024 3 distantly related families with (NM_000482.4):c.196C>G, p.Leu66Val, 2 distantly related families with c.97G>A, p.Asp33Asn. Method: WGS. Affected individuals presented with chronic kidney disease, with mean age of kidney failure of 64.5 years. Kidney biopsies from affected individuals showed amyloid deposits in the medulla, with Apoa4 protein being the main constituent. p.Leu66Val - 3 heterozygotes in gnomAD v4.1.0 (European), Revel score = 0.27 p.Asp33Asn - not in gnomAD v4, though p.Asp33Glu and p.Asp33Val have been reported; Revel score = 0.31 PMID: 33751222 Murakami et al., 2021 Report of a 68 yo Japanese man, with 4 variants in APOA4: 2 synonymous (p.Thr29Thr, p.Leu128Leu); '6981A>C',p.Asn248Thr; and c.743A>C, p.Asn248Thr - not in gnomAD v4. Only APOA4 was sequenced. Patient had history of renal cysts, diagnosed with HCM 2 years prior. Authors highlight that Apoa4 protein aggregation is causal, but the gene variant may not be. PMID: 27262366 Dasari et al. 2016 Reported 11 patients with Apolipoprotein A-IV associated amyloidosis (mean age at diagnosis 63.5yrs). Biopsies showed large amounts of eosinophilic Congo–red positive amyloid deposits restricted to the renal medulla. ApoA-IV protein was the most abundant peptide in the amyloid deposits. However, molecular analysis was performed in only 2/11 patients, and no APOA4 mutations were found. PMID: 21900878 Sethi et al., 2012 52yo man with CKD and amyloid deposits in the medulla, harbouring 3 common, likely benign APOA4 variants: c.548G>A, p.(Thr29Thr); c.1678G>A, p.(Ser147Asn); c.2378G>T, p.(Gln380His). He also carried 2 APOA1 variants: c.60T>C, p.(His20His) - synonymous, not in gnomAD; c.209T>C, p.(Leu70Pro) - missense, not in gnomAD v4. APOA1 more likely to be causal? Only sequenced these 2 genes. Conflicting functional evidence: PMID: 39699959 Nakamura et al., 2024: TFEB downregulation in aged mice leads to APOA4 amyloidosis - variants in other genes may cause APOA4 to aggregate. APOA4 is linked to Tubulointerstitial kidney disease, autosomal dominant 6, MIM: 621106 (OMIM accessed 18th Dec 2025). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v1.11 | APOA1 | Sarah Leigh changed review comment from: It would appear that certain heterozygous APOA1 variants are associated with Amyloidosis, 3 or more types OMIM:105200 (PMID 32022753, table 1).; to: It would appear that certain heterozygous APOA1 variants are associated with Amyloidosis, 3 or more types OMIM:105200 (PMID 32022753, 24 variants listed in table 1). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v1.11 | APOA1 | Sarah Leigh edited their review of gene: APOA1: Added comment: It would appear that certain heterozygous APOA1 variants are associated with Amyloidosis, 3 or more types OMIM:105200 (PMID 32022753, table 1).; Changed rating: GREEN; Changed publications to: 32022753 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v1.11 | APOA1 | Sarah Leigh Publications for gene: APOA1 were set to 27240838; 21820994; 16925563 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v1.10 | APOA1 |
Sarah Leigh Added comment: Comment on mode of inheritance: Both biallelic and monoallelic variants have been associated with ApoA-I and apoC-III deficiency, combined OMIM:618463; Hypoalphalipoproteinemia, primary, 2, with or without corneal clouding OMIM:618463;hypoalphalipoproteinemia, primary, 2 MONDO:0032766 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v1.10 | APOA1 | Sarah Leigh Mode of inheritance for gene: APOA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v1.9 | APOA1 | Sarah Leigh Phenotypes for gene: APOA1 were changed from Amyloidosis, 3 or more types 105200 to Amyloidosis, 3 or more types OMIM:105200; familial visceral amyloidosis MONDO:0007099 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v0.14 | APOA1 | Eleanor Williams Phenotypes for gene: APOA1 were changed from 105200 to Amyloidosis, 3 or more types 105200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v0.7 | APOA1 |
Eleanor Williams commented on gene: APOA1: Associated with Amyloidosis, 3 or more types (#105200) in OMIM. More than 3 cases reported. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v0.4 | APOA1 | Eleanor Williams reviewed gene: APOA1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21820994, 16925563, 27240838; Phenotypes: 105200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary systemic amyloidosis v0.3 | APOA1 |
Eleanor Williams gene: APOA1 was added gene: APOA1 was added to Amyloidosis. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: APOA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: APOA1 were set to 27240838; 21820994; 16925563 Phenotypes for gene: APOA1 were set to 105200 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||