Analysis of the TTR gene in the investigation of amyloidosis: A 25-year single UK center experience.
Dorota Rowczenio, Candida C Quarta, Marianna Fontana, Carol J Whelan, Ana Martinez-Naharro, Hadija Trojer, Anna Baginska, Stuart M Ferguson, Janet Gilbertson, Tamer Rezk, Sajitha Sachchithanantham, Shameem Mahmood, Richa Manwani, Faye Sharpley, Ashutosh D Wechalekar, Philip N Hawkins, Julian D Gillmore, Helen J Lachmann
Author Information
Dorota Rowczenio: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK. ORCID
Candida C Quarta: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Marianna Fontana: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Carol J Whelan: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Ana Martinez-Naharro: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Hadija Trojer: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Anna Baginska: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Stuart M Ferguson: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Janet Gilbertson: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Tamer Rezk: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Sajitha Sachchithanantham: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Shameem Mahmood: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Richa Manwani: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Faye Sharpley: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Ashutosh D Wechalekar: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Philip N Hawkins: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Julian D Gillmore: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
Helen J Lachmann: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
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.
