CRYAB in Hypertrophic Cardiomyopathy (HCM)

Evidence for role of CRYAB in HCM

A detailed analysis of the role of non-sarcomeric genes in HCM - incorporating clinical sequencing data from the OMGL and LMM labs, a cohort of over 800 HCM probands from the Royal Brompton Hospital, London and the National Heart Centre, Singapore (sequenced on a broad cardiac NGS panel) and published sequencing, segregation and functional data - has clarified the involvement of CRYAB variants in this condition (see our study published in the European Heart Journal for further details).

Based on this analysis, CRYAB is classified as having: Moderate Evidence


Case excess (gene)Max LOD scoreCase excess (variant)De novo variant
non-significant- -
See details below p.Q26X (PMID:23197161)

Cohort (reference)HCM patients testedRare variantsCase FrequencySignificance vs ExAC
28082330 804 2 0.00249 p=0.684
Total 804 2 0.00249 p=0.684

Summary of the frequency of rare CRYAB variants (ExAC frequency < 0.0001) in published cohorts of HCM probands. P-values shown are from Fisher' Exact test compared to rare variants in ExAC (ExAC frequency = 0.00208). Significance is based on multiple testing correction of 31 genes tested (p<0.0016).



References

1. Roddy Walsh, Rachel Buchan, Alicja Wilk, Shibu John, Leanne E. Felkin, Kate L. Thomson, Tang Hak Chiaw, Calvin Chin Woon Loong, Chee Jian Pua, Claire Raphael, Sanjay Prasad, Paul J. Barton, Birgit Funke, Hugh Watkins, James S. Ware, Stuart A. Cook. Defining the genetic architecture of hypertrophic cardiomyopathy: re-evaluating the role of non-sarcomeric genes. Eur Heart J. 2017 doi:10.1093/eurheartj/ehw603.