Renal apolipoprotein A-I amyloidosis associated with a novel mutant Leu64Pro

Murphy, Charles L.; Wang, Shuching; Weaver, Kristal; Gertz, Morie A.; Weiss, Deborah; Solomon, Alan

doi:10.1053/j.ajkd.2004.08.033

Cited by 42 publications

(33 citation statements)

References 31 publications

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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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“…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%

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

Rowczenio

Doğan

Theis

et al. 2011

The American Journal of Pathology

112

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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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“…A total of 12 amyloidogenic apoA-I variants have been identified to date. 10 The natural history of the disease consists of progressive liver and kidney involvement with restrictive cardiomyopathy observed in some variants. We recently referred to an amyloidogenic variant of apoA-I associated with a predominantly sporadic presentation, in which the leucine residue at position 75 is replaced by proline (Leu75Pro).…”

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Infertility and Hypergonadotropic Hypogonadism as First Evidence of Hereditary Apolipoprotein A-I Amyloidosis

et al. 2007

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Purpose:We report that primary infertility and hypergonadotropic hypogonadism in young patients may be caused by testicular amyloidosis and it is associated with the presence of a mutation in the apoA-I gene, resulting in the replacement of proline for leucine at residue 75 of the protein. Materials and Methods:Ten patients presenting with infertility, gynecomastia, decreased libido, erectile dysfunction or a family history of amyloidosis underwent clinical evaluation, hormone assays, semen analysis, ultrasonographic investigation of the testicles, testicular biopsy and DNA sequencing of the apoA-I gene. Results: All patients showed azoospermia and 9 had increased testicular volume. Massive amyloid deposition was observed in all testicular biopsies and the apoA-I mutation of replacement of proline for leucine at residue 75 of the protein was noted. Five patients showed hypergonadotropic hypogonadism and 5 had normal testosterone values with high gonadotropin levels. Conclusions: Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid deposits and genetic analysis of apoA-I mutations are recommended in young, infertile patients with macro-orchidism. Finally, surveillance in asymptomatic mutation carriers is suggested to evaluate the opportunity to implement sperm retrieval and start androgen replacement therapy when necessary.

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Renal apolipoprotein A-I amyloidosis associated with a novel mutant Leu64Pro

Cited by 42 publications

References 31 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

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

Infertility and Hypergonadotropic Hypogonadism as First Evidence of Hereditary Apolipoprotein A-I Amyloidosis

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