Amyloid deposits in the proband, one of the transplanted individuals, were composed of apolipoprotein A-I (apoA-I), and among living family members there was complete concordance between amyloidosis and the presence of a novel 9 base pair in-frame deletion mutation in exon 4 of the apoA-I gene, causing a loss of residues Glu70Phe71Trp72.
The new insights in the understanding of the association of apoA-I with HDL, its metabolism, and its hypothesized structural findings may explain a common mechanism for the genesis of apoA-I induced amyloidosis.
The aim of this study was to evaluate the extent of amyloid deposits in explanted livers from two patients with apolipoprotein A-Iamyloidosis, with the Arg26 mutation, to determine their suitability as domino donors.
While the spectrum of APOA1 mutations provides no particular mechanistic insights, molecular diagnosis may still be important due to clinical differences between amyloidosis resulting from mutation in APOA1 vs. other genes.
Apolipoprotein A-Iamyloidosis (AApo A-I) is an inherited systemic disease that results from pathologic deposition in tissues of fibrils composed of Apo A-I-related molecules.
Described is the clinical and histologic picture of renal involvement as a result of apolipoprotein A-Iamyloidosis in five families of Italian ancestry.
We describe six patients with AApoAI amyloidosis due to APOA1 germline mutations that affect the larynx, small intestine, large intestine, heart, liver, kidney, uterus, ovary, or pelvic lymph nodes.
ApoA-I variants with amino acid substitutions, especially in the region of amino acid residues 50-93 and 170-178, have been associated with amyloidosis.
The clinical spectrum and outcome of hereditary apolipoprotein A-Iamyloidosis are reviewed in detail and support the need for sequencing of the apolipoprotein A-I gene among patients with apparent localized amyloidosis in whom IHC is nondiagnostic of the fibril protein, even in the absence of a family history of disease.
The X-ray crystal structure of the C-terminal truncated human protein, Δ(185-243)apoA-I, determined to 2.2 Å resolution by Mei and Atkinson, provides the structural basis for understanding apoA-I destabilization in amyloidosis.
Second, 0.27% of individuals in the general population were heterozygous for NS variants which were associated with substantial reductions in apoA-I (up to 39 mg/dL) and/or HDL cholesterol (up to 0.9 mmol/L) and, surprisingly, 0.41% were heterozygous for variants predisposing to amyloidosis.
On the other hand, aortic stiffness was significantly greater in patients with APO A-I amyloidosis than controls (PWV 11.5 ± 2.9 and 10.7 ± 2.3 m/s, p < 0.05), even after adjusting for confounders.
Apo AIamyloidosis is characterized by slowly progressive renal disease and end-stage renal disease occurs aproximately 3 to 15 years from initial diagnosis.