Identification of TAZ mutation in a family with X-linked dilated cardiomyopathy by Next Generation Sequencing

Abstract

Familial dilated cardiomyopathy (DCM) is defined as DCM of unknown cause in 2 or more closely related family members. We reported a family with 2 male siblings both presented with heart failure in infancy and subsequently confirmed to have DCM without conduction abnormalities. Endo-myocardial biopsy (in the elder sibling), extensive metabolic workup, viral studies and NimbleGen CGX-12 array were all normal. Oligonucleotide-based target capture (Sureselect, Agilent) followed by next generation sequencing (Illumina HiSeq2000) was used to capture variants of 46 genes implicated in the causation of cardiomyopathy (Partners Healthcare Center for Personalized Genetic Medicine). Clinically significant /novel variants are confirmed by independent Sanger sequencing. A hemizygous variant c.718G>C (p.Gly240Arg) in exon 10 of TAZ gene is identified. This variant is likely pathogenic as it has been reported in 5 individuals with X-linked infantile DCM and was described in a family with endocardial fibroelastosis. So far, the 2 siblings did not show evidence of skeletal myopathy, stunted growth, neutropenia or abnormal urine organic acid analysis. Next generation sequencing (NGS) allows efficient screening of a panel of genes in complex disorders like DCM, in which there is substantial overlap among phenotypes, multiple causative genes, and some mutations associated with > 1 phenotype. The identification of TAZ mutation has major impact in the medical surveillance of our patients as they need to be monitored for symptoms of Barth syndrome in addition to DCM.