Copy number variants implicate cardiac function and development pathways in earthquake-induced stress cardiomyopathy.

Area of Science:

• Cardiology
• Genetics
• Pathophysiology

Background:

• Stress cardiomyopathy (SCM), or takotsubo syndrome, is a poorly understood cardiac condition.
• SCM often occurs sporadically after stressful events, but familial clusters have been reported.
• The underlying genetic predisposition to SCM remains largely unknown.

Purpose of the Study:

• To investigate potential genetic predisposition models for stress cardiomyopathy.
• To analyze genetic factors in women who developed SCM following major natural disasters.

Main Methods:

• Exome analysis
• Genotyping array analysis
• Array comparative genomic hybridization
• Analysis of 28 women with SCM after Christchurch earthquakes.

Main Results:

• A high rate of rare, heterogeneous copy number variants (CNVs) of uncertain clinical significance was observed in 12/28 subjects.
• Several CNVs impacted genes with cardiac relevance (e.g., RBFOX1, GPC5, KCNRG, CHODL, GPBP1L1).
• No physical overlap or apparent functional relationship was found between the identified CNVs and impacted genes.

Conclusions:

• SCM predisposition may be linked to a high incidence of rare CNVs.
• This finding offers a novel perspective on the enigmatic pathophysiology of stress cardiomyopathy.
• Further research into genetic factors could elucidate SCM etiology.