Dilated Cardiomyopathy via the LAMA4 Gene

Dilated cardiomyopathy (DCM) is a heterogeneous disease of the cardiac muscle. It is characterized by dilatation of the left, right, or both ventricles, systolic dysfunction, and diminished myocardial contractility. Symptoms include arrhythmia, dyspnea, chest pain, palpitation, fainting, and congestive heart failure (Ikram et al. 1987). Additional features may include woolly hair and myopathy (Møller et al. 2009). Sudden death occurs in ~30% of patients with DCM (Tamburro and Wilber 1992). Although symptoms of DCM usually begin in adulthood, an extensive clinical variability between individuals concerning the age of onset, penetrance, and extent of structural and functional abnormality has been documented. The prevalence of DCM has been estimated at ~1/2700 (Codd et al. 1989).

Up to 30% of DCM cases are familial (Grünig et al. 1998). In about half of these families, DCM is inherited in an autosomal dominant manner (AD-DCM). In rare families, the disease is transmitted with an autosomal recessive, X-linked or mitochondrial inheritance. AD-DCM is caused by defects in genes encoding myocardial proteins, including LAMA4. LAMA4 encodes protein Laminin, Alpha 4, which is a member of extracellular matrix glycoproteins. Laminins are thought to mediate the attachment, migration and organization of cells during development. LAMA4 pathogenic variants disrupt the interaction between LAMA4 and intergrin molecules, which may cause cardiomyopathy and heart failure (Knöll et al. 2007). So far, all causative variants reported in LAMA4 are missense (Human Gene Mutation Database).

Detection rate of pathogenic variants in the LAMA4 gene in a large cohort of patients is unknown in the literature because only a limited number of cases have been reported.

This test provides full coverage of all coding exons of the LAMA4 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).