Open AccessA novel de novo CASZ1 heterozygous frameshift variant causes dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy
Author(s) -
Guo Jun,
Li Zheng,
Hao Chanjuan,
Guo Ruolan,
Hu Xuyun,
Qian Suyun,
Zeng Jiansheng,
Gao Hengmiao,
Li Wei
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.828
Subject(s) - dilated cardiomyopathy , exome sequencing , frameshift mutation , cardiomyopathy , proband , left ventricular noncompaction , sanger sequencing , medicine , genetics , compound heterozygosity , mutation , cardiology , exome , heart failure , biology , gene
Abstract Background Dilated cardiomyopathy (DCM) is the most common cardiomyopathy with a common presentation of heart failure. It has been reported that CASZ1 loss‐of‐function mutation contributes to familial DCM and congenital ventricular septal defect (VSD). To date, only two pathogenic variants in CASZ1 have been previously reported worldwide. Methods To identify the causative variant in an 11‐month‐old Chinese boy with DCM and left ventricular noncompaction cardiomyopathy (LVNC), trio‐whole‐exome sequencing was performed followed by mutational analysis and Sanger sequencing. Results An unreported de novo heterozygous frameshift variant (c.2443_2459delGTGGGCAAGCCT, p.Val815Profs*14) in CASZ1 was idenitified in the proband. The frameshift mutation in CASZ1 not only led to DCM but also presented an LVNC phenotype. Conclusion We have identified a novel CASZ1 variant in a patient with combined DCM and LVNC for the first time, thus broadening the phenotypic spectrum of CASZ1 variants. Furthermore, this study emphasized the usefulness of whole‐exome sequencing for genetic diagnosis of cardiomyopathy.