Next Article in Journal
Mechanisms of Enhancer-Promoter Interactions in Higher Eukaryotes
Next Article in Special Issue
Summary of the Available Molecular Methods for Detection of SARS-CoV-2 during the Ongoing Pandemic
Previous Article in Journal
Interplay between Abscisic Acid and Gibberellins, as Related to Ethylene and Sugars, in Regulating Maturation of Non-Climacteric Fruit
Previous Article in Special Issue
Genetic Insight into the Domain Structure and Functions of Dicer-Type Ribonucleases
Open AccessCase Report

Clinical Considerations for a Family with Dilated Cardiomyopathy, Sudden Cardiac Death, and a Novel TTN Frameshift Mutation

1
Department of Arrhythmology, IRCCS Policlinico San Donato, Piazza Edmondo Malan 1, San Donato Milanese, 20097 Milan, Italy
2
Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy
3
Vita-Salute San Raffaele University, 20132 Milan, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(2), 670; https://doi.org/10.3390/ijms22020670
Received: 27 November 2020 / Revised: 31 December 2020 / Accepted: 5 January 2021 / Published: 12 January 2021
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)
Dilated cardiomyopathy (DCM) is the leading indication for heart transplantation. TTN gene truncating mutations account for about 25% of familial DCM cases and for 18% of sporadic DCM cases. The clinical relevance of specific variants in TTN has been difficult to determine because of the sheer size of the protein for which TTN encodes, as well as existing extensive genetic variation. Clinicians should communicate novel clinically-relevant variants and genotype–phenotype associations, so that animal studies evaluating the molecular mechanisms are always conducted with a focus on clinical significance. In the present study, we report for the first time the novel truncating heterozygous variant NM_001256850.1:c.72777_72783del (p.Phe24259Leufs*51) in the TTN gene and its association with DCM in a family with sudden death. This variant occurs in the A-band region of the sarcomere, in a known mutational hotspot of the gene. Truncating titin variants that occur in this region are the most common cause of DCM and have been rarely reported in asymptomatic individuals, differently from other pathogenic TTN gene variants. Further studies are warranted to better understand this particular clinically-relevant variant. View Full-Text
Keywords: dilated cardiomyopathy; TTN; titin; sudden cardiac death; genetic testing; mutation; humans; family; deletion; truncating dilated cardiomyopathy; TTN; titin; sudden cardiac death; genetic testing; mutation; humans; family; deletion; truncating
Show Figures

Figure 1

MDPI and ACS Style

Micaglio, E.; Monasky, M.M.; Bernardini, A.; Mecarocci, V.; Borrelli, V.; Ciconte, G.; Locati, E.T.; Piccoli, M.; Ghiroldi, A.; Anastasia, L.; Pappone, C. Clinical Considerations for a Family with Dilated Cardiomyopathy, Sudden Cardiac Death, and a Novel TTN Frameshift Mutation. Int. J. Mol. Sci. 2021, 22, 670. https://doi.org/10.3390/ijms22020670

AMA Style

Micaglio E, Monasky MM, Bernardini A, Mecarocci V, Borrelli V, Ciconte G, Locati ET, Piccoli M, Ghiroldi A, Anastasia L, Pappone C. Clinical Considerations for a Family with Dilated Cardiomyopathy, Sudden Cardiac Death, and a Novel TTN Frameshift Mutation. International Journal of Molecular Sciences. 2021; 22(2):670. https://doi.org/10.3390/ijms22020670

Chicago/Turabian Style

Micaglio, Emanuele; Monasky, Michelle M.; Bernardini, Andrea; Mecarocci, Valerio; Borrelli, Valeria; Ciconte, Giuseppe; Locati, Emanuela T.; Piccoli, Marco; Ghiroldi, Andrea; Anastasia, Luigi; Pappone, Carlo. 2021. "Clinical Considerations for a Family with Dilated Cardiomyopathy, Sudden Cardiac Death, and a Novel TTN Frameshift Mutation" Int. J. Mol. Sci. 22, no. 2: 670. https://doi.org/10.3390/ijms22020670

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop