Cardiac conduction alterations in a French family with amyloidosis of the finnish type with the p.Asp187Tyr mutation in the <i>GSN</i> gene

Chastan, Nathalie; Baert‐Desurmont, Stéphanie; Saugier-Veber, Pascale; Dérumeaux, Geneviève; Cabot, Annick; Frébourg, Thierry; Hannequin, Didier

doi:10.1002/mus.20448

Cited by 47 publications

(37 citation statements)

References 31 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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%

“…In fact, patients homozygous for the amyloidogenic mutation of gelsolin develop a severe nephrotic syndrome and, ultimately, end stage renal failure (Maury, 1993). Cardiac involvement, including conduction abnormalities, is also sometimes seen (Chastan et al, 2006, Kiuru et al, 1994). Ultimately, further amyloid deposition in vital organs and microvasculature can become life threatening, and the primary causes of death are typically nephrotic syndrome, pneumonia from aspiration due to bulbar muscle dysfunction, or cerebral hemorrhage likely from cerebral angiopathy (Kiuru, 1998).…”

Section: Clinical Presentations Of Familial Amyloidosis Of Finnish Typementioning

confidence: 99%

See 1 more Smart Citation

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

Solomon

Page

Balch

et al. 2012

Critical Reviews in Biochemistry and Molecular Biology

View full text Add to dashboard Cite

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.

show abstract

Section: History and Epidemiology Of Gelsolin Amyloidosismentioning

confidence: 99%

Section: Clinical Presentations Of Familial Amyloidosis Of Finnish Typementioning

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

View full text Add to dashboard Cite

show abstract

“…The most common, a G to A transition at nucleotide 654, has been detected in all Finnish patients as well as in families of other nationalities (2,7,9) . The second mutation, a G to T transversion at nucleotide 654, has been detected in 3 different families, and is related to the Danish type of familial amyloidosis, first described in 1979 by Boysen et al (2,(7)(8)(9) In this study we describe for the first time a G654T mutation in the gelsolin gene in a Brazilian family. The clinical features of this subtype are very similar to those described by Meretoja (FAF), presenting skin and neurological changes associated with lattice corneal dystrophy (2,(9)(10)(11) .…”

Section: Discussionmentioning

confidence: 99%

“…This mutation has been reported in all Finnish patients as well as in other countries. The second mutation is a 654G-T transversion resulting in a Asp187Tyr substitution and was found in only three families, of Danish, Czech and French origins, with similar clinical manifestations (1,2,(4)(5)(6)(7)(8) . We report the first case in a Brazilian family, carrying the Asp187Tyr mutation, with no known Finnish ancestors.…”

Section: Introductionmentioning

confidence: 99%

Danish type gelsolin-related amyloidosis in a Brazilian family: case reports

Solari¹,

Ventura²,

Antecka³

et al. 2011

Arq. Bras. Oftalmol.

View full text Add to dashboard Cite

Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant form of systemic amyloidosis showing marked geographic clustering in Finland. The disease is caused by a point mutation, 654G-A, in the gelsolin gene. The Danish-subtype of FAF has been previously described in three families, the patients present clinical findings similar to FAF, and the mutation 654G-T in the gelsolin gene. Three members from two generations of the same family, with familial amyloidosis, were screened for mutations in the GSN gene. Genomic DNA was extracted from peripheral blood lymphocytes and the polymerase chain reaction (PCR) was carried out under standard conditions, using appropriate primers. Sequence analysis showed the presence of a G to T transition at nucleotide 654 of the gelsolin gene. This is the first report of gelsolin-related familial amyloidosis in a Brazilian family, and the result is particularly significant as this pedigree presents an unusual mutation, described previously in three families, with no known Finnish ancestors (Danish type). Keywords

show abstract

“…62 However, in rare cases, severe autonomic dysfunction can occur as was reported in a French family with cardiac sympathetic dysfunction. 63 Other organs may be involved, including the heart, kidneys, brain, and spinal cord. 64 …”

Section: Transthyretin Amyloidosismentioning

confidence: 99%

The Neuromuscular Manifestations of Amyloidosis

Simmons

Specht²

2010

Journal of Clinical Neuromuscular Disease

View full text Add to dashboard Cite

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.

show abstract

Cardiac conduction alterations in a French family with amyloidosis of the finnish type with the p.Asp187Tyr mutation in the GSN gene

Cited by 47 publications

References 31 publications

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

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

Danish type gelsolin-related amyloidosis in a Brazilian family: case reports

The Neuromuscular Manifestations of Amyloidosis

Contact Info

Product

Resources

About