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Anna Gärtner-Rommel, Jens Tiesmeier, Thomas Jakob, Bernd Strickmann, Gunter Veit, Bernd Bachmann-Mennenga, Lech Paluszkiewicz, Karin Klingel, Uwe Schulz, Kai Thorsten Laser, Bernd Karger, Heidi Pfeiffer, Hendrik Milting

• \(\bf Background\) Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy with a prevalence of about 1:200. It is characterized by left ventricular hypertrophy, diastolic dysfunction and interstitial fibrosis; HCM might lead to sudden cardiac death (SCD) especially in the young. Due to low autopsy frequencies of sudden unexplained deaths (SUD) the true prevalence of SCD and especially of HCM among SUD remains unclear. Even in cases of proven SCD genetic testing is not a routine procedure precluding appropriate risk stratification and counseling of relatives. \(\bf Methods\) Here we report a case of SCD in a 19‐year‐old investigated by combined forensic and molecular autopsy. \(\bf Results\) During autopsy of the index‐patient HCM was detected. As no other possible cause of death could be uncovered by forensic autopsy the event was classified as SCD. Molecular autopsy identified two (probably) pathogenic genetic variants in \(\it FHL1\) and MYBPC3. The \(\it MYBPC3\) variant had an incomplete penetrance. The \(\it FHL1\) variant was a de novo mutation. We detected reduced \(\it FHL1\) mRNA levels and no \(\it FHL1\) protein in muscle samples suggesting nonsense‐mediated mRNA decay and/or degradation of the truncated protein in the SCD victim revealing a plausible disease mechanism. \(\bf Conclusion\) The identification of the genetic cause of the SCD contributed to the rational counseling of the relatives and risk assessment within the family. Furthermore our study revealed evidences for the pathomechanism of \(\it FHL1\) mutations.