Relevance of Truncating Titin Mutations in Dilated Cardiomyopathy

[PUBLICATION] Clin Genet. 2016 Jan 18. doi: 10.1111/cge.12741.

As a continuation to Blueprint Genetics recent collaborative studies on genetics of dilated cardiomyopathy (DCM) (Eur Heart J 2015 and PlosOne 2015), we performed meta-analysis of truncating titin variants in DCM. Others and we have previously estimated TTN truncating variants (TTNtv) – nonsense, frameshift and consensus splice site, to be responsible for 18-25% of familial cases of DCM and 11-15% of sporadic cases in large patient cohorts (Herman et al. 2012, Roberts et al. 2015, Haas et al. 2015, Akinrinade et al. 2015 and Akinrinade et al. 2016). However, clinical interpretation of these variants is known to be challenging, as these variants are also present rarely in reference populations. Our previous study showed that one in 500 individuals carries a truncation in TTN A-band suggesting that the penetrance of these potentially harmful variants is still not fully understood (Akinrinade et al. 2015). Thus, further research was warranted.

Akinrinade O, Koskenvuo JW, Alastalo TP

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