Rare variant (p.Ser43Asn) of familial transthyretin amyloidosis associated with isolated cardiac phenotype: A case series with literature review.
Alleles
Amino Acid Substitution
Amyloid Neuropathies, Familial
/ complications
Biomarkers
Cardiomyopathies
/ diagnosis
Echocardiography
Electrocardiography
Family
Female
Genetic Association Studies
Genetic Predisposition to Disease
Heart Function Tests
Humans
Italy
Male
Middle Aged
Mutation
Pedigree
Phenotype
Prealbumin
/ genetics
Single Photon Emission Computed Tomography Computed Tomography
Symptom Assessment
ATTR
amyloidosis
cardiomyopathy
transthyretin
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
25
11
2020
received:
28
08
2020
accepted:
30
11
2020
pubmed:
22
12
2020
medline:
24
3
2022
entrez:
21
12
2020
Statut:
ppublish
Résumé
p.Ser43Asn is a very rare transthyretin (TTR) mutation leading to familial amyloidosis of transthyretin type, ATTR amyloidosis. It was previously observed in four patients worldwide and is associated almost invariably with an isolated cardiac phenotype. We report here on an Italian family with early-onset cardiomyopathy and aggressive disease course in the affected individuals leading untreated to cardiac death before 55 years of age. We describe the clinical phenotype and imaging findings of two affected siblings, who were treated with tafamidis at an early disease stage, and their affected mother, who died 9 years ago due to refractory heart failure. The review of the available literature highlights the fact that until recently ATTR amyloidosis may have been misdiagnosed as other types of hypertrophic cardiomyopathy. A better characterization of the genotype-phenotype associations is crucial to achieve optimal outcomes and facilitate informed decisions when treating individuals with rare mutations.
Sections du résumé
BACKGROUND
p.Ser43Asn is a very rare transthyretin (TTR) mutation leading to familial amyloidosis of transthyretin type, ATTR amyloidosis. It was previously observed in four patients worldwide and is associated almost invariably with an isolated cardiac phenotype.
METHODS AND RESULTS
We report here on an Italian family with early-onset cardiomyopathy and aggressive disease course in the affected individuals leading untreated to cardiac death before 55 years of age. We describe the clinical phenotype and imaging findings of two affected siblings, who were treated with tafamidis at an early disease stage, and their affected mother, who died 9 years ago due to refractory heart failure. The review of the available literature highlights the fact that until recently ATTR amyloidosis may have been misdiagnosed as other types of hypertrophic cardiomyopathy.
CONCLUSION
A better characterization of the genotype-phenotype associations is crucial to achieve optimal outcomes and facilitate informed decisions when treating individuals with rare mutations.
Identifiants
pubmed: 33345470
doi: 10.1002/mgg3.1581
pmc: PMC8683619
doi:
Substances chimiques
Biomarkers
0
Prealbumin
0
TTR protein, human
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1581Informations de copyright
© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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