Three Newly Recognized Likely Pathogenic Gene Variants Associated with Hereditary Transthyretin Amyloidosis.
Neurol Ther
; 11(4): 1595-1607, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-35933469
ABSTRACT
INTRODUCTION:
Hereditary transthyretin amyloidosis (ATTRv [variant]) is a clinically heterogeneous, progressively debilitating, fatal disease resulting from the deposition of insoluble amyloid fibrils in various organs and tissues. Early diagnosis of ATTRv can be facilitated with genetic testing; however, such testing of the TTR gene identifies variants of uncertain significance (VUS) in a minority of cases, a small percentage of which have the potential to be pathogenic. The Akcea/Ambry VUS Initiative is dedicated to gathering molecular, clinical, and inheritance data for each TTR VUS identified by genetic testing programs to reclassify TTR variants to a clinically actionable status (e.g., variant likely pathogenic [VLP]) where appropriate.METHODS:
Classification criteria used here, based on recommendations from the American College of Medical Genetics and Genomics, are stringent and comprehensive, requiring distinct lines of evidence supporting pathogenesis.RESULTS:
Three TTR variants have been reclassified from VUS to VLP, including c.194C>T (p.A65V), c.172G>C (p.D58H), and c.239C>T (p.T80I). In each case, the totality of genetic, structural, and clinical evidence provided strong support for pathogenicity.CONCLUSIONS:
Based on several lines of evidence, three TTR VUS were reclassified as VLP, resulting in a high likelihood of disease diagnosis for those and subsequent patients as well as at-risk family members.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Guideline
/
Prognostic_studies
/
Risk_factors_studies
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Screening_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article