Gelsolin‐related familial amyloidosis, Finnish type, in a Portuguese family: Clinical and neurophysiological studies

Conceição, Isabel; Sales-Luis, M.L.; Carvalho, Mamede de; Evangelista, Teresinha; Fernandes, Rui; Paunio, Tiina; Kangas, Hannele; Coutinho, Paula; Marques-Neves, Carlos; Saraiva, Maria João

doi:10.1002/mus.10474

Cited by 32 publications

(27 citation statements)

References 25 publications

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“…Since the first report of the disease, patients have been found in many countries, including the United States, Japan, Portugal, England, Germany, Spain, France, Brazil, Sweden, Denmark, the Czech Republic, and Iran. (Conceicao et al, 2003, Pihlamaa et al, 2011, Huerva et al, 2007, Stewart et al, 2000, Ikeda et al, 2007, Tanskanen et al, 2007, Chastan et al, 2006, Contegal et al, 2006, Luettmann et al, 2010, Ardalan et al, 2007, Makioka et al, 2010, Kiuru, 1998, Carrwik and Stenevi, 2009, Felix et al, 2008, Plante-Bordeneuve and Said, 2011). Many of the patients studied had no Finnish ancestors, suggesting multiple founders of the disease.…”

Section: History and Epidemiology Of Gelsolin Amyloidosismentioning

confidence: 99%

Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention

Solomon

Page

Balch

et al. 2012

Critical Reviews in Biochemistry and Molecular Biology

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Protein misassembly into aggregate structures, including cross-β-sheet amyloid fibrils, is linked to diseases characterized by the degeneration of post-mitotic tissue. While amyloid fibril deposition in the extracellular space certainly disrupts cellular and tissue architecture late in the course of amyloid diseases, strong genetic, pathological and pharmacologic evidence suggests that the process of amyloid fibril formation itself, known as amyloidogenesis, likely causes these maladies. It seems that the formation of oligomeric aggregates during the amyloidogenesis process causes the proteotoxicity and cytotoxicity characteristic of these disorders. Herein, we review what is known about the genetics, biochemistry and pathology of familial amyloidosis of Finnish Type (FAF) or gelsolin amyloidosis. Briefly, autosomal dominant D187N or D187Y mutations compromise Ca2+ binding in domain 2 of gelsolin, allowing domain 2 to sample unfolded conformations. When domain 2 is unfolded, gelsolin is subject to aberrant furin endoproteolysis as it passes through the Golgi on its way to the extracellular space. The resulting C-terminal 68kDa fragment (C68) is susceptible to extracellular endoproteolytic events, possibly mediated by a matrix metalloprotease, affording 8 and 5 kDa amyloidogenic fragments of gelsolin. These amyloidogenic fragments deposit systemically, causing a variety of symptoms, including corneal lattice dystrophy and neurodegeneration. The first murine model of the disease recapitulates the aberrant processing of mutant plasma gelsolin, amyloid deposition, and the degenerative phenotype. We use what we have learned from our biochemical studies, as well as insight from mouse and human pathology to propose therapeutic strategies that may halt the progression of FAF.

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Section: History and Epidemiology Of Gelsolin Amyloidosismentioning

confidence: 99%

Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention

Solomon

Page

Balch

et al. 2012

Critical Reviews in Biochemistry and Molecular Biology

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“…Prominent motor involvement has been rarely reported but was present in 2 of 13 cases ( Rajani et al, 2000 ) , in a case of FAP from Japan with homozygous TTR Met30 mutation ( Yoshioka et al, 2001 ) , and in an Italian patient presenting with motor neuron disease ( Quattrini et al, 1998 ) . Familial cases due to mutation in the gelsolin gene have been studied in Finland, with amyloid deposits visible in the perineurium and vessel walls ( Kiuru‐Enari et al, 2002 ) , and in a few other countries ( Conceiçao et al, 2003 ) .…”

Section: Discussionmentioning

confidence: 99%

Amyloid neuropathy: a retrospective study of 35 peripheral nerve biopsies

Vital

Bouillot-Eimer

et al. 2004

J Peripheral Nervous Sys

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We performed a retrospective study of 35 peripheral nerve biopsies (PNBs) with amyloid deposits in the endoneurium. In every case, nerve lesions were studied on paraffin-embedded fragments (PEFs) and by ultrastructural examination (USE). In addition, muscle fragments were taken and embedded in paraffin. Immunohistochemistry was performed with anti-transthyretin (TTR) serum on 19 nerve and 15 muscle PEFs. Direct immunofluorescence with anti-light-chain sera was performed on frozen nerve fragments in 19 cases. Endoneurial amyloid deposits were easily identified on routine PEF in 26 cases, after Congo red or thioflavine staining in three, and by USE in six. A dramatic myelinated fiber loss was evidenced in 34 cases (77-2970 per mm2), and features of axonal degeneration were present in every case. Segmental demyelination was observed in 10 cases. A mutation in the TTR gene was present in 14 cases, with Met30 mutation in 10 and Ala49 in four members of the same family. Amyloid deposits were strongly marked by the anti-TTR serum in 11 other cases, twice in the endoneurium, five around muscle fibers, and four in both locations. In eight patients, light-chain positivity was evidenced in endoneurial deposits, lambda in six and kappa in two. Two other patients with monoclonal gammopathy did not present any light-chain fixation. In 17 cases, amyloidosis was disclosed by PNB and 13 had a TTR pathology; eight of them, over 65 years old, correspond to a late-onset form of familial amyloid polyneuropathy which is an underdiagnosed condition.

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“…Subsequently, families have been described in several European countries, the United States, and Japan. [51][52][53][54][55][56][57][58] Inheritance is autosomal-dominant. The main clinical features are cranial neuropathies, corneal lattice dystrophy, a laxity of the skin termed cutis laxa, and peripheral neuropathy, which may be associated with an autonomic neuropathy.…”

Section: Transthyretin Amyloidosismentioning

confidence: 99%

The Neuromuscular Manifestations of Amyloidosis

Simmons

Specht²

2010

Journal of Clinical Neuromuscular Disease

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Amyloidosis is a systemic disease that may be acquired or hereditary and which results in the deposition of amyloid fibrils in a variety of tissues causing their progressive dysfunction. Although the clinical presentation often is dominated by cardiac or renal failure, peripheral neuropathy may be a significant or the initial manifestation, resulting in presentation to the neurologist. Diagnosis often is challenging and may require multiple diagnostic procedures, including more than one biopsy. Acquired and hereditary amyloidosis can be definitively distinguished from one another only by immunohistochemical staining or molecular genetic testing. Treatment remains a challenge, although chemotherapy and autologous stem cell transplantation offer hope for those with primary systemic amyloidosis, whereas liver transplantation is effective for some forms of hereditary amyloid neuropathy. Much less commonly, myopathy may be a clinically significant manifestation of amyloidosis.

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Gelsolin‐related familial amyloidosis, Finnish type, in a Portuguese family: Clinical and neurophysiological studies

Cited by 32 publications

References 25 publications

Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention

Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention

Amyloid neuropathy: a retrospective study of 35 peripheral nerve biopsies

The Neuromuscular Manifestations of Amyloidosis

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