DSG2 Variant Linked to Severe Cardiomyopathy Cases
Author Information
Author(s): Takuya Sumida, Shou Ogawa, Higo Shuichiro, Yuki Kuramoto, Ryo Eto, Yoshihiko Ikeda, Congcong Sun, Junjun Li, Li Liu, Tomoka Tabata, Yoshihiro Asano, Mikio Shiba, Yasuhiro Akazawa, Daisuke Nakamura, Takafumi Oka, Tomohito Ohtani, Yasushi Sakata
Primary Institution: Osaka University
Hypothesis
The pathological significance and prevalence of the heterozygous DSG2 p.Arg119Ter variant in cardiomyopathy patients remains uncertain.
Conclusion
The DSG2 p.Arg119Ter variant is more common in East Asian populations and may worsen heart conditions when combined with other genetic or environmental factors.
Supporting Evidence
- Four unrelated patients with heterozygous DSG2 p.Arg119Ter variants were identified among 808 patients with nonischemic cardiomyopathy.
- The allele frequency of the DSG2 p.Arg119Ter variant was found to be 0.0037, significantly higher than in the general Japanese population.
- Immunohistochemical analysis revealed reduced expression of desmoglein-2 and desmoplakin in myocardial samples.
- Transmission electron microscopy showed abnormal desmosomes and gaps in intercalated discs in the myocardium of affected patients.
- Microforce tests indicated reduced contractility in iPSC-CMs carrying the heterozygous DSG2 variant.
Takeaway
This study found a gene variant that can cause serious heart problems in some patients, showing that it might be more common in certain populations.
Methodology
The study involved genetic analysis of 808 patients with nonischemic cardiomyopathy, identifying variants through whole-exome sequencing and immunohistochemical analysis.
Limitations
The study cannot exclude the possibility of noncoding intronic and intergenic variants that may be associated with known cardiomyopathy-causing genetic variants.
Participant Demographics
The study included four unrelated patients with cardiomyopathy, identified among 808 patients diagnosed with nonischemic cardiomyopathy.
Statistical Information
P-Value
0.0037
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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