Tabulation of human transthyretin (TTR) variants, 2003

Connors, Lawreen H.; Lim, Amareth; Prokaeva, Tatiana; Roskens, Violet; Costello, Catherine E.

doi:10.3109/13506120308998998

Cited by 448 publications

(380 citation statements)

References 5 publications

Supporting

Mentioning

358

Contrasting

Unclassified

Order By: Relevance

“…All TTR variants which lead to the formation of amyloid fibrils are accompanied by one amino acid substitution. To date, more than 100 mutations have been identified as a causative gene abnormality in ATTR type FAP (40). The clinical phenotype of this In the Val30MetATTR type it was previously thought that, although the patients in endemic areas showed a high incidence of various ECG abnormalities with conduction disturbances, which frequently required the implantation of a pacemaker, they rarely suffered from cardiac amyloidosis with congestive heart failure (41-43).…”

Section: Hereditary Amyloidosismentioning

confidence: 99%

See 1 more Smart Citation

Cardiac Amyloidosis: Heterogenous Pathogenic Backgrounds

Ikeda

2004

Intern. Med.

View full text Add to dashboard Cite

Cardiac amyloidosis is a fatal disorder which develops on the basis of the different pathologic conditions in systemic amyloidosis: the most common underlying disease is immunoglobulin light chain-derived primary amyloidosis and the next is transthyretin-related hereditary amyloidosis; the latter disorder, typically represented by familial amyloid polyneuropathy, was long regarded as an endemic disease. However, this disorder has now been shown to involve a highly variable clinical picture due to a large number of transthyretin gene mutations, and many patients with diverse ancestors suffer from severe cardiac amyloidosis. Additionally, senile systemic amyloidosis is now noted as a cause of cardiac dysfunction in elderly individuals. Echocardiogram and myocardial technetium-99m-pyrophosphate scintigraphy can provide characteristic findings. Immunohistochemistry on tissue amyloid, biochemical analysis of serum and urine proteins, and DNA sequencing are usually employed to determine the disease-related amyloid fibril protein.Although systemic amyloidosis has become treatable, the prognosis of each patient who received up-to-date and effective, but nevertheless stressful, therapy depends on the severity of cardiac involvement by amyloid deposition.

show abstract

Section: Hereditary Amyloidosismentioning

confidence: 99%

“…Moreover, it has been shown that many ATTRs produce hereditary amyloidosis with a predominant clinical manifestation of cardiac amyloidosis (Fig. 2) (Table 3) (40). Most patients with non-Val30Met ATTRs had a later age of onset and usually lacked an apparent family history.…”

Section: Hereditary Amyloidosismentioning

confidence: 99%

Cardiac Amyloidosis: Heterogenous Pathogenic Backgrounds

Ikeda

2004

Intern. Med.

View full text Add to dashboard Cite

show abstract

“…10 To date, 4120 transthyretin mutations have been identified, most of which lead to development of familial amyloidotic polyneuropathy; transthyretin Val30Met is the most common disease-causing transthyretin mutation in the world. 11,12 Although clinical disorders of typical familial amyloidotic polyneuropathy patients, including peripheral neuropathy, autonomic dysfunction, renal dysfunction, gastrointestinal disorders, and ocular manifestations, are different from those of patients with senile systemic amyloidosis, several transthyretin variants such as transthyretin Val122Ile cause a cardiac amyloidosis that mimics senile systemic amyloidosis. 13 The importance of accurate diagnosis of senile systemic amyloidosis has been increasingly recognized, and a novel specific transthyretin stabilizer, tafamidis, has been developed and is undergoing phase II and III clinical trials.…”

mentioning

confidence: 99%

Clinicopathological features of senile systemic amyloidosis: an ante- and post-mortem study

et al. 2011

View full text Add to dashboard Cite

Senile systemic amyloidosis is a common age-related amyloidosis that involves accumulation of wild-type transthyretin, with cardiac dysfunction being a predominant result. The importance of obtaining an accurate diagnosis of senile systemic amyloidosis has been increasingly recognized, so that novel treatments are being developed. However, the clinicopathological features of senile systemic amyloidosis remain to be completely understood. Here, we evaluated cardiac specimens from 181 consecutive post-mortem cases older than 40 years, including 6 cases of senile systemic amyloidosis, and 5 cases of familial amyloidotic polyneuropathy, which is a hereditary systemic amyloidosis caused by mutant forms of transthyretin. Furthermore, we studied ante-mortem clinicopathological findings of 11 senile systemic amyloidosis cases, in which 9 cases underwent gastrointestinal tract biopsy and/or subcutaneous tissue biopsy, at Kumamoto University Hospital. Of the autopsied cases of elderly Japanese (older than 80 years), 12% had senile systemic amyloidosis, with the percentage increasing with age. The occurrence of senile systemic amyloidosis in elderly Japanese patients was lower than that in previous reports, which suggests that a genetic background and/or environmental factor(s) may have important roles in the occurrence of senile systemic amyloidosis. Transthyretin amyloid deposits in familial amyloidotic polyneuropathy cases developed mainly in the pericardium and the surrounding muscle fascicles, whereas in cases with senile systemic amyloidosis the transthyretin amyloid deposits had a patchy plaque-like shape and developed mainly inside the ventricular wall. Biopsies from senile systemic amyloidosis patients evidenced amyloid deposits in 44% (4/9) of gastrointestinal tract and subcutaneous tissue samples combined. As myocardial biopsy may be dangerous for elderly people, the use of a combination of gastrointestinal tract and subcutaneous tissue biopsies may make diagnosis of senile systemic amyloidosis easier.

show abstract

“…Sometimes a severe cardiomyopathy is the initial presentation of the disease. 10 There is also a nonfamilial acquired form of ATTR amyloidosis. In this disease of old-aged men (rarely women), nonmutated (wild-type) TTR can also act as an amyloid precursor by a still unknown mechanism.…”

Section: Types Of Amyloidosismentioning

confidence: 99%

“…Nonspecific complaints such as fatigue and weight loss gradually appear and can be debilitating, but are often noticed only after disease progression leads to more specific signs, such as edema, dyspnea, bleeding, or orthostatic hypotension. A limited overview of the diverse disease manifestations of the main types of amyloidosis 4,[7][8][9][10]24 is presented in this section.…”

Section: Disease Manifestationsmentioning

confidence: 99%