Age and Sex Differences in the Genetics of Cardiomyopathy

• DOI: 10.1007/s12265-023-10411-8
• Publication Date: 2023-07-21T15:02:05Z
• Authors: Oyediran Akinrinade; Robert Lesurf; ; J. C. Ambrose; P. Arumugam; M. Bleda; F. Boardman-Pretty; C. R. Boustred; H. Brittain; M. J. Caulfield; G. C. Chan; T. Fowler; A. Giess; A. Hamblin; S. Henderson; T. J. P. Hubbard; R. Jackson; L. J. Jones; D. Kasperaviciute; M. Kayikci; A. Kousathanas; L. Lahnstein; S. E. A. Leigh; I. U. S. Leong; F. J. Lopez; F. Maleady-Crowe; L. Moutsianas; M. Mueller; N. Murugaesu; A. C. Need; P. O‘Donovan; C. A. Odhams; C. Patch; D. Perez-Gil; M. B. Pereira; J. Pullinger; T. Rahim; A. Rendon; T. Rogers; K. Savage; K. Sawant; R. H. Scott; A. Siddiq; A. Sieghart; S. C. Smith; A. Sosinsky; A. Stuckey; M. Tanguy; E. R. A. Thomas; S. R. Thompson; A. Tucci; E. Walsh; M. J. Welland; E. Williams; K. Witkowska; S. M. Wood; Jane Lougheed; Tapas Mondal; John Smythe; Luis Altamirano-Diaz; Erwin Oechslin; Seema Mital
• Keywords: Penetrance; Dilated Cardiomyopathy; LMNA

Abstract Cardiomyopathy has variable penetrance. We analyzed age and sex-related genetic differences in 1,397 cardiomyopathy patients (Ontario, UK) with whole genome sequencing. Pediatric cases (n = 471) harbored more deleterious protein-coding variants Tier 1 genes compared to adults 926) (34.6% vs 25.9% respectively, p 0.0015), variant enrichment constrained coding regions. had a higher burden of sarcomere lower channelopathy gene adults. Specifically, pediatric MYH7 MYL3 hypertrophic cardiomyopathy, fewer TTN truncating dilated cardiomyopathy. clustered the myosin head neck domains children. OBSCN was top mutated adults, enriched for protein-truncating variants. In female z-disc males. Genetic may explain variability Genotype-guided predictions onset can inform pre-test counseling. Graphical were likely be genotype-positive than MYH7, MYL3, TNNT2, VCL . Adults Females (DCM)