A novel TTN deletion in a family with skeletal myopathy, facial weakness, and dilated cardiomyopathy.
TTN
dilated cardiomyopathy
myopathy
variant interpretation
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:
11 2019
11 2019
Historique:
received:
24
05
2019
revised:
12
07
2019
accepted:
26
07
2019
pubmed:
7
9
2019
medline:
1
7
2020
entrez:
7
9
2019
Statut:
ppublish
Résumé
Pathogenic variants in TTN (OMIM 188840), encoding the largest human protein, are known to cause dilated cardiomyopathy and several forms of skeletal myopathy. The clinical interpretation of TTN variants is challenging, however, due to the frequency of missense changes, variable testing and reporting practices in commercial laboratories, and incomplete understanding of the spectrum of TTN-related disease. We report a heterozygous TTN deletion segregating in a family with an unusual skeletal myopathy phenotype associated with facial weakness, gait abnormality, and dilated cardiomyopathy. A novel 16.430 kb heterozygous deletion spanning part of the A- and M-bands of TTN was identified in the proband and his symptomatic son, as well as in an additional son whose symptoms were identified on clinical evaluation. The deletion was found to be de novo in the proband. Pathogenic variants in TTN may be an unrecognized cause of skeletal myopathy phenotypes, particularly when accompanied by dilated cardiomyopathy.
Sections du résumé
BACKGROUND
Pathogenic variants in TTN (OMIM 188840), encoding the largest human protein, are known to cause dilated cardiomyopathy and several forms of skeletal myopathy. The clinical interpretation of TTN variants is challenging, however, due to the frequency of missense changes, variable testing and reporting practices in commercial laboratories, and incomplete understanding of the spectrum of TTN-related disease.
METHODS
We report a heterozygous TTN deletion segregating in a family with an unusual skeletal myopathy phenotype associated with facial weakness, gait abnormality, and dilated cardiomyopathy.
RESULTS
A novel 16.430 kb heterozygous deletion spanning part of the A- and M-bands of TTN was identified in the proband and his symptomatic son, as well as in an additional son whose symptoms were identified on clinical evaluation. The deletion was found to be de novo in the proband.
CONCLUSION
Pathogenic variants in TTN may be an unrecognized cause of skeletal myopathy phenotypes, particularly when accompanied by dilated cardiomyopathy.
Identifiants
pubmed: 31489791
doi: 10.1002/mgg3.924
pmc: PMC6825852
doi:
Substances chimiques
Connectin
0
TTN protein, human
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e924Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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