Clinical exome sequencing revealed that FLNC variants contribute to the early diagnosis of cardiomyopathies in infant patients

Background: FLNC encodes actin-binding protein and is mainly concentrated in skeletal and cardiac muscle. Mutations in FLNC were found in cardiomyopathies. To date, studies on FLNC-cardiomyopathies have mainly been reported in adults. There are limited studies that have investigated FLNC variants in pediatric patients with cardiomyopathies. Methods: We summarized the patients who carried rare variants of FLNC from May 2016 to May 2019 in the Center for Molecular Medicine, Children’s Hospital of Fudan University, from clinical exome sequencing data. Results: A total of 5 patients with FLNC rare variants were included. Of them, 3 were male and 2 were female. The median age was 3 months (range from 19 days to 30 months). A1186V was a known pathogenic variant reported in pediatric patients with cardiomyopathy (PMID: 29858533), and the other four variants were novel. In the four novel variants, there are one splicing (c.2265+4del) and three missense (p.R441I, p.C1639Y, and p.A2648S). Two patients (patients 1 and 3) were diagnosed with restrictive cardiomyopathy, two patients (patients 2 and 5) were diagnosed with dilated cardiomyopathy, and one patient (patient 4) was diagnosed with arrhythmia. Conclusions: All five patients have survived to date. In summary, FLNC rare variants identified by clinical exome sequencing provide genetic evidence to make early diagnosis of cardiomyopathy in infant patients.