Disease relevance of Amyloidosis, Familial

• In familial amyloidosis of the Finnish type (FAF), or gelsolin-related amyloidosis, the amyloid subunit protein consists of gelsolin peptides of amino acids 173-243 with the disease causing substitution at Asp187 [1].
• A family with hereditary amyloidosis characterized by peripheral neuropathy and cardiomyopathy is described [2].
• Familial amyloid polyneuropathy is an hereditary amyloidosis related to several different genetic errors [3].
• Amyloid fibril protein in familial amyloidosis with cranial neuropathy and corneal lattice dystrophy (FAP type IV) is related to transthyretin [4].
• Familial amyloidotic polyneuropathy (FAP), Portuguese type, is a hereditary amyloidosis caused by mutated transthyretin (ATTR) in which an exchange of valine for methionine at position 30 has taken place (ATTR Val30Met) [5].

Psychiatry related information on Amyloidosis, Familial

• Amyloid diseases like Alzheimer's disease and familial amyloidosis of Finnish type (FAF) stem from endoproteolytic cleavage of a precursor protein to generate amyloidogenic peptides that accumulate as amyloid deposits in a tissue-specific manner [6].

High impact information on Amyloidosis, Familial

• This is the first demonstration of hereditary amyloidosis associated with a variant fibrinogen alpha-chain [7].
• Dominantly inherited familial amyloidosis, Finnish type (FAF) is caused by the accumulation of a 71-amino acid amyloidogenic fragment of mutant gelsolin (GSN) [8].
• Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187 [8].
• In addition to causing a new phenotype, this is the first deletion mutation to be described in association with hereditary amyloidosis and it significantly extends the value of the apoAI model for investigation of molecular mechanisms of amyloid fibrillogenesis [9].
• In the last several years, five human plasma prealbumin (transthyretin) variants have been discovered in association with hereditary amyloidosis, a late-onset fatal disorder [10].

Chemical compound and disease context of Amyloidosis, Familial

• Furin initiates gelsolin familial amyloidosis in the Golgi through a defect in Ca(2+) stabilization [11].
• Autosomal dominant hereditary amyloidosis with a unique cutaneous and cardiac presentation and death from heart failure by the sixth or seventh decade was found to be associated with a previously unreported point mutation (thymine to cytosine, nt 1389) in exon 4 of the apolipoprotein A1 (apoA1) gene [12].
• The Asp 187-->Asn (D187N) Asp 187-->Tyr (D187Y) gelsolin mutations facilitate two proteolytic cuts in the parent protein generating a 71-residue fragment that forms amyloid fibrils in humans, putatively causing Finnish type familial amyloidosis (FAF) [13].
• One-third of the molecules had the same amino acid substitution, methionine for valine in position 30, as in familial amyloidosis of Portuguese, Japanese and Swedish-American type [14].
• Cardiac technetium-99m pyrophosphate scintigraphy in familial amyloidosis [15].

Biological context of Amyloidosis, Familial

• Recent molecular studies demonstrated eight distinct amyloid-associated point mutations in the prealbumin gene on the long arm of chromosome 18 that are associated with hereditary amyloidosis [16].
• The results show that the amyloid fibril protein in Finnish hereditary amyloidosis represents a new type of amyloid protein that shows amino acid sequence homology with gelsoline, an actin-modulating protein [17].
• Molecular genetic studies revealed a heterozygous codon 55 point mutation, resulting in a proline for leucine-substitution, a mutation previously associated with aggressive familial amyloidosis in a US kindred of Dutch and German descent [18].
• Tissue distribution of amyloid deposits in Abyssinian cats with familial amyloidosis [19].

Anatomical context of Amyloidosis, Familial

• Hereditary familial amyloidosis of Finnish type (FAF) leading to amyloid in the peripheral and central nervous systems stems from deposition of a 71 residue fragment generated from the D187N/Y variants of plasma gelsolin by two sequential endoproteolytic events [11].
• Autonomic nervous system and cardiac involvement in familial amyloidosis, Finnish type (FAF) [20].
• Transthyretin-related TTR hereditary amyloidosis of the vitreous body. Clinical and molecular characterization in two Italian families [21].
• Formalin-fixed paraffin sections of livers, spleens and kidneys from patients with primary, secondary and familial amyloidosis as well as from a casein-induced murine amyloid model were analysed by an immunocytochemical (unlabeled antibody enzyme) method utilizing antisera to amyloid-related proteins [22].

Gene context of Amyloidosis, Familial

• Gelsolin domain 2 Ca2+ affinity determines susceptibility to furin proteolysis and familial amyloidosis of finnish type [23].
• In the group with familial amyloidosis, however, the lower than normal levels of prealbumin did not correspond to elevations in C-reactive protein and serum amyloid A. Our data suggest that depressed plasma prealbumin concentrations noted in individuals with familial amyloidosis are not simply reflections of a negative acute-phase response [24].
• Liver biopsy discloses a new apolipoprotein A-I hereditary amyloidosis in several unrelated Italian families [25].
• These findings show that prealbumin and RBP serum concentrations are depressed in patients with the Indiana type of hereditary amyloidosis and that these serum abnormalities may be present long before development of clinical disease [26].
• Five proteins--transthyretin, fibrinogen alpha-A chain, apolipoprotein AI, lysozyme, apolipoprotein AII, cystatin C and gelsolin--can be associated with hereditary amyloidosis involving the kidney [27].

Analytical, diagnostic and therapeutic context of Amyloidosis, Familial

• Twenty-eight patients with amyloid heart disease, 9 with primary and 19 with familial amyloidosis, were examined by Doppler echocardiography to characterize transmitral flow velocity patterns and to assess restrictive ventricular hemodynamics [28].

References