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Analysis of the TTR gene in the investigation of amyloidosis: A 25‐year single UK center experience
Author(s) -
Rowczenio Dorota,
Quarta Candida C.,
Fontana Marianna,
Whelan Carol J.,
MartinezNaharro Ana,
Trojer Hadija,
Baginska Anna,
Ferguson Stuart M.,
Gilbertson Janet,
Rezk Tamer,
Sachchithanantham Sajitha,
Mahmood Shameem,
Manwani Richa,
Sharpley Faye,
Wechalekar Ashutosh D.,
Hawkins Philip N.,
Gillmore Julian D.,
Lachmann Helen J.
Publication year - 2019
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23669
Subject(s) - transthyretin , amyloidosis , single center , medicine , biology , amyloid (mycology) , pathology
Transthyretin amyloidosis (ATTR) is caused by deposition of either wild‐type (ATTRwt) or variant (ATTRm) transthyretin. ATTRwt presents with restrictive cardiomyopathy, while ATTRm displays a range of organ involvement. This retrospective analysis includes all patients referred to a single UK center in the last 25 years for clinical and laboratory assessment of known or suspected amyloidosis who underwent TTR gene sequencing. A total of 4459 patients were included in this study; 37% had final diagnosis of ATTR amyloidosis; 27% light chain amyloidosis; 0.7% other types of amyloidosis; 21.3% had no amyloid and 14% had no data. TTR variants were found in 770 (17%) cases; the most prevalent were p.V142I, p.T80A, and p.V50M identified in 42, 25, and 16%, respectively. The median age at referral in each group was: 76 (range 47–93), 66 (40–81), and 45 years (21–86), respectively. Overall 42 rare or novel variants were identified. Forty‐two percent patients with ATTRm died at a median age of 73 years (33–89) with a median survival from diagnosis of 50 months. ATTRwt was the final diagnosis in 20% of patients undergoing genetic testing. Our findings of TTR variants in 17% of screened patients highlight the need for routine genetic testing in the evaluation of suspected ATTR amyloidosis.