Left Ventricular Noncompaction 8

A number sign (#) is used with this entry because of evidence that left ventricular noncompaction-8 (LVNC8) and dilated cardiomyopathy-1LL (CMD1LL) are caused by heterozygous mutation in the PRDM16 gene (605557) on chromosome 1p36.

For a general phenotypic description and a discussion of genetic heterogeneity of left ventricular noncompaction, see LVNC1 (604169).

For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200).

Arndt et al. (2013) described 3 patients with left ventricular noncompaction who were found to have mutations in the PRDM16 gene (see MOLECULAR GENETICS). The first patient was a man who presented at 33 years of age with severe biventricular heart failure with systolic and diastolic dysfunction, secondary pulmonary hypertension, and dilation of both atria and ventricles. Echocardiography showed involvement of apical and lateral segments, with marked thickening of the inferior noncompacted layer below the left ventricular papillary muscles and thinning of the compacted layer. He received a biventricular intracardiac defibrillator. The second patient, who was diagnosed at 12 years of age due to arrhythmias, showed mild to moderate left ventricular dysfunction and dilation in addition to LVNC. Echocardiography showed involvement of the left midventricular lateral wall. The third patient was a man who underwent reconstruction of a dysplastic mitral valve due to grade 3 mitral insufficiency at 11 years of age, at which time the left atrium and ventricle were enlarged with preserved cardiac function. Histology of a left ventricular biopsy taken at surgery showed increased interstitial fibrosis and myocyte disarray.

In 17 of 18 patients with a deletion in chromosome 1p36 (see 607872) who showed evidence of heart muscle disease (left ventricular noncompaction or cardiomyopathy), Arndt et al. (2013) aligned the regions of chromosomal loss and identified a shared deleted interval at chr1:3,224,674-3,354,772 bp (GRCh37) that involved only a single gene, PRDM16. Sequencing of the PRDM16 gene in 75 probands previously diagnosed with LVNC (Klaassen et al., 2008; Probst et al., 2011) identified 3 probands with heterozygous mutations (605557.0001-605557.0003) that were not present in 156 controls or in the 1000 Genomes Project database. Analysis by RNA-seq of 131 explanted heart biopsy samples from patients with dilated cardiomyopathy who underwent transplantation revealed 4 additional variants in the PRDM16 gene in 5 patients (see, e.g., 605557.0004-605557.0006), which were confirmed by Sanger sequencing of genomic DNA from peripheral blood.