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| Mendeliome v1.2317 | APOA4 | Zornitza Stark Phenotypes for gene: APOA4 were changed from Hereditary amyloidosis, MONDO:0018634, APOA4-related to Hereditary amyloidosis, MONDO:0018634, APOA4-related; Tubulointerstitial kidney disease, autosomal dominant 6, MIM# 621106 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2316 | APOA4 | Zornitza Stark edited their review of gene: APOA4: Changed phenotypes: Hereditary amyloidosis, MONDO:0018634, APOA4-related, Tubulointerstitial kidney disease, autosomal dominant 6, MIM# 621106 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2130 | APOA4 | Zornitza Stark Marked gene: APOA4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2130 | APOA4 | Zornitza Stark Gene: apoa4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2130 | APOA4 | Zornitza Stark Classified gene: APOA4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2130 | APOA4 | Zornitza Stark Gene: apoa4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2129 | APOA4 |
Zornitza Stark gene: APOA4 was added gene: APOA4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: APOA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: APOA4 were set to 38096951 Phenotypes for gene: APOA4 were set to Hereditary amyloidosis, MONDO:0018634, APOA4-related Review for gene: APOA4 was set to GREEN Added comment: 5 families with autosomal dominant medullary amyloidosis. WGS/WES identified 2 different variants in the APOA4 gene (p.D33N in 3 families and p.L66V in 2 families). The variants were absent in gnomAD, located at the structurally flexible N-terminal domain of APOA4, and segregated with disease. There were 48 genotype +ve individuals with 44/48 having an eGFR <60. All clinically affected individuals presented with a bland urinary sediment, CKD, and no clinical evidence of systemic amyloidosis. Mean age of dialysis/transplantation was 58+/-11yrs. Routine kidney biopsies limited to the kidney cortex showed tubulointerstitial fibrosis and secondary glomerulosclerosis and no amyloid deposition. Four affected individuals were shown to have isolated medullary deposition of amyloid, with mass spectrometry showing the mutated Apoa4 as the primary constituent in 3 available cases. Plasma total ApoA4 levels were increased for patients (n=15) with ApoA4 mutations versus controls (n=49). They hypothesize that the amino acid substitutions alter the tertiary or quaternary structure of the mutated ApoA4, leading to increased plasma and primary urine concentrations and isolated medullary amyloid deposition. Sources: Literature |
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