Identification of a missense mutation in the melusin-encoding ITGB1BP2 gene in a patient with dilated cardiomyopathy

In a heterogeneous cohort of patients (n = 255) with sporadic and familial dilated cardiomyopathy (DCM), we searched for novel disease-associated mutations in the human melusin-encoding ITGB1BP2 gene and found only one missense mutation, which was a substitution of alanine for glycine at position 313 located in the carboxy-terminal spacer region of the molecule. This point mutation (c.938C>G) was identified in a 45-year-old male with familial DCM and severe impairment of left-ventricular function, but was absent in 300 healthy control subjects. However, its functional significance in the context of heart failure is unclear, as this amino acid substitution was predicted to be without disease-causing effects. In this report, we confirm the low prevalence of mutations and single nucleotide polymorphisms in the coding sequence of the human melusin gene in patients with DCM, ruling out the possibility that genetic variations in this myocardially transcribed gene may have a significant impact on the epidemiology of DCM-induced heart failure.

► In a cohort of n = 255 DCM patients we searched for mutations in the melusin gene.
► A novel missense mutation was identified in the carboxy-terminal spacer region.
► The p.A313G mutation was associated with severe left-ventricular dysfunction.
► No melusin mutations were detected in 300 healthy control subjects.
► Melusin mutations have only limited epidemiologic significance in human DCM.