Hereditary nephropathic systemic amyloidosis caused by a novel variant apolipoprotein A-I

Persey, M.R.; Booth, David R.; Booth, SE; Zyl-Smit, Raul van; Adams, Brett; Fattaar, Abe B.; Tennent, Glenys A.; Hawkins, Philip N.; Pepys, Mark B.

doi:10.1046/j.1523-1755.1998.00770.x

Cited by 71 publications

(43 citation statements)

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“…3 More than 50 natural variants of ApoA-I have been described, and a little over one third are associated with familial amyloidosis, with 19 known mutations in the APOA1 gene. 2,[4][5][6][7][8][9] Eriksson et al have described different patterns of organ involvement by hereditary ApoA-1 amyloidosis based on specific mutations in hot-spot regions of the APOA1 gene: Mutations in coding regions 50-93 were more likely to cause hepatic and renal involvement, whereas mutations in regions 173-178 were more prone to cardiac, laryngeal, and cutaneous involvement. 10 In addition, the peptide comprising residues 46-59 forms amyloidlike fibrils, and researchers have suggested that this region is responsible for selfrecognition, aggregation, and overall amylogenic propensity of ApoA-1 amyloid.…”

Section: Discussionmentioning

confidence: 99%

Renal ApoA-1 Amyloidosis with Glu34Lys Mutation and Intra-amyloid Lipid Accumulation

Andeen

Lam

Nicosia

2014

Journal of the American Society of Nephrology

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Apolipoprotein A-1 (ApoA-1) amyloidosis occurs as a nonhereditary condition in atherosclerotic plaques, but it can also manifest as a hereditary disorder caused by mutations of the APOA1 gene. Hereditary ApoA-1 amyloidosis presents with diverse organ involvement based on the position of the mutation. We describe a case of ApoA-1 amyloidosis with a Glu34Lys mutation; testicular, conjunctival, and renal involvement; and the notable finding of lipid deposition within the amyloid deposits.

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Section: Discussionmentioning

confidence: 99%

Renal ApoA-1 Amyloidosis with Glu34Lys Mutation and Intra-amyloid Lipid Accumulation

Andeen

Lam

Nicosia

2014

Journal of the American Society of Nephrology

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“…Given the ability to perform protein phenotyping assays rapidly and on small amounts of blood (with no PCR intermediate step), economically competitive MSIA (i.e., pennies per assay) can be constructed to screen populations for polymorphisms/mutations already correlated to disease. Presently, apoE phenotypes have been linked most significantly to Alzheimer's disease and coronary heart disease (20)(21)(22), and a limited number of apoA-I mutations have been linked to amyloidosis (14,(23)(24)(25)(26). Assaying these and other mutations will find use in proteomic applications geared toward understanding the biological processes underlying the (protein) phenotype-related diseases.…”

Section: Apoe Phenotyping and Possible Applicationsmentioning

confidence: 99%

Novel mass spectrometric immunoassays for the rapid structural characterization of plasma apolipoproteins

Niederkofler

Tubbs

Kiernan

et al. 2003

Journal of Lipid Research

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Novel mass spectrometric immunoassays (MSIAs) for the isolation and structural characterization of plasma apolipoprotein A-I (apoA-I), apoA-II, and apoE have been developed. The assays combine selective isolation of apolipoprotein species via affinity capture with mass-specific detection using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In application, plasma (from 50 l of whole blood drawn from individuals, using finger lancet) was addressed with affinity pipette tips derivatized with antibodies toward the specific apolipoprotein. The time required for each assay was ‫ف‬ 15 min, less if assays on multiple individuals were performed in parallel. In a brief study of five individuals, several recently reported apoA-II variants were identified and observed consistently in all individuals. Additionally, the apoE phenotype of E3/ E3 was observed in three of the individuals, and E2/E3 and E3/E4 observed in the remaining two individuals, the latter of whom suffers from Alzheimer's disease. Overall, the MSIA approach offers a rapid, sensitive, and highly accurate means of profiling apolipoproteins from small volumes of plasma. The apolipoproteins represent a significant class of proteins whose functions range from enzyme activation (e.g., LCAT and lipoprotein lipase) to lipid/cholesterol transport and clearance. Although well studied over the past two decades, it has only recently become clear that mutations present within the apolipoproteins may be responsible for, or assist in, the progression of disease. Table 1 gives a brief overview of some diseases correlated with specific mutations present within apolipoproteins. Universally, these mutations are commonly studied on the DNA level using a variety of genotyping assays. For instance, apolipoprotein E (apoE) genotyping usually involves PCR amplification of short subsequences of exons 2 and 3 (containing both polymorphic sites) and analysis of the PCR products by: 1 ) dot blot hybridization with allele-specific oligonucleotide probes (1); 2 ) oligonucleotide ligation assay (2); 3 ) single-stranded conformational polymorphisms (3); or, 4 ) restriction fragment-length polymorphism analysis using restriction enzymes recognizing the sites of polymorphism (4). More advanced approaches involve competitive amplified single mutation detection by selective probe hybridization immunoassay (5) or primer-extension mass spectrometry assays directed at the polymorphic sites within the gene (6). This latter assay brings to the analysis the direct detection of indicators (extended primers containing the base complement of the polymorphism) at exact mass values, thus enabling an assay that is free of artifacts encountered in other assays using, e.g., electrophoretic gel shifts or differential hybridization.As with the nucleic acid mass spectrometry assays, direct mass spectrometric analysis of proteins (or proteolytic fragments) brings an unprecedented degree of analytical accuracy to the analysis of point mutations. However, whereas the polym...

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“…105200) was coined by Ostertag 1 in 1932 following the discovery of two families with dominantly inherited renal amyloidosis. Mutations in the genes encoding apolipoprotein A-I (apoAI), [2][3][4][5][6][7][8][9][10][11][12] apolipoprotein A-II (apoAII), 13 fibrinogen A␣-chain, 14 -17 and lysozyme 18 have since been identified as the cause of hereditary renal amyloidosis in different kindreds (Online Mendelian Inheritance of Man no. 105200).…”

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confidence: 99%

“…Patients with hereditary apoAI amyloidosis typically present with hypertension, proteinuria, and renal impairment 6 and frequently develop extensive visceral deposits that affect the liver, spleen, and kidneys, with occasional involvement of the heart, nerves, larynx, and gastrointestinal tract. Although the condition may lead to end-stage renal disease and other organ failure, the natural history of the disease is often slow, contrasting systemic AL amyloidosis in which the median patient survival without therapy is approximately 6 to 15 months from diagnosis.…”

mentioning

confidence: 99%

Amyloidogenicity and Clinical Phenotype Associated with Five Novel Mutations in Apolipoprotein A-I

Rowczenio

Doğan

Theis

et al. 2011

The American Journal of Pathology

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113

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The phenotype of hereditary apolipoprotein A-I amyloidosis is heterogeneous with some patients developing extensive visceral amyloid deposits and end-stage renal failure as young adults and others having only laryngeal and/or skin amyloid, which may be of little clinical consequence. Clinical management and prognosis of patients with systemic amyloidosis depend entirely on correct identification of the fibril protein, such that light chain amyloidosis (AL, previously referred to as "primary"), the most frequently diagnosed type, is treated with chemotherapy, which has absolutely no role in hereditary apolipoprotein A-I amyloidosis. We report five novel apolipoprotein A-I variants, four of which were amyloidogenic and one of which was incidental in a patient with systemic AL amyloidosis. Interestingly, only one of four patients with apolipoprotein A-I amyloidosis had a family history of similar disease. Amyloidosis is a rare disorder characterized by extracellular deposition of fibrillar protein that results in a progressive disruption of structure and function of affected tissues and organs. Amyloidosis is a remarkably heterogeneous disease; it can be acquired or hereditary and systemic or localized.The most common form of systemic amyloidosis is AL (light chain, previously referred to as "primary"), in which the fibrils are derived from monoclonal immunoglobulin light chains and consist of the whole or part of the variable (V L ) domain. The prognosis of systemic AL amyloidosis is generally worse than in other amyloid types, although there is marked heterogeneity in the extent of organ involvement and rate of disease progression. Treatment of AL amyloidosis is with chemotherapy for which there is no role in other amyloid types.Hereditary systemic amyloidosis is a rare autosomal dominant condition caused by deposition of variant proteins as amyloid fibrils. The term "hereditary nonneuropathic systemic amyloidosis" (Online Mendelian Inheritance of Man no. 105200) was coined by Ostertag 1 in 1932 following the discovery of two families with dominantly inherited renal amyloidosis. Mutations in the genes encoding apolipoprotein A-I (apoAI), 2-12 apolipoprotein A-II (apoAII), 13 fibrinogen A␣-chain, 14 -17 and lysozyme 18 have since been identified as the cause of hereditary renal amyloidosis in different kindreds (Online Mendelian Inheritance of Man no. 105200). The clinical amyloidosis syndromes that accompany the various mutations in these different genes are diverse with respect to age at onset, mode of presentation, pattern of organ distribution, rate of progression, and prognosis. Indeed, certain apoAI variants are associated with neuropathy 19,20 such that the nomenclature, which includes the term "nonneuropathic," is confusing and probably no longer appropriate.Supported by the UK Department of Health.Accepted for publication June 15, 2011.The licensed patent rights to perform protein extraction from paraffinembedded tissue for the mass spectrometry-based amyloid typing test were granted by Expression Patholo...

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Hereditary nephropathic systemic amyloidosis caused by a novel variant apolipoprotein A-I

Cited by 71 publications

References 9 publications

Renal ApoA-1 Amyloidosis with Glu34Lys Mutation and Intra-amyloid Lipid Accumulation

Renal ApoA-1 Amyloidosis with Glu34Lys Mutation and Intra-amyloid Lipid Accumulation

Novel mass spectrometric immunoassays for the rapid structural characterization of plasma apolipoproteins

Amyloidogenicity and Clinical Phenotype Associated with Five Novel Mutations in Apolipoprotein A-I

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