Centronuclear Myopathy-3, Autosomal Dominant via the MYF6 Gene

An apparently rare form of autosomal dominant centronuclear myopathy (CNM3; OMIM 614408) has been found to be caused by mutations in the MYF6 gene (Kerst et al. Neuromuscul Disord 10:572-577, 2000). A single patient has been described with elevated serum CpK levels at the age of 9 years. At the age of 12 years the patient complained of exercise induced muscle cramps and weakness in his slower limbs. At this stage, serum CpK levels were normal, however, a muscle biopsy revealed myopathic changes with increased numbers of centrally placed nuclei.

Centronuclear myopathy is a genetically heterogeneous disorder. One X-linked form and several autosomal dominant forms are known. MYF6-related centronuclear myopathy is inherited as an autosomal dominant disorder. The one patient described with CNM3 was found to have a missense mutation of a conserved amino acid in the helix 1 region of myogenic transcription factor-6 protein. In vitro studies showed that protein-protein interaction of the mutant protein was reduced, and potential to bind to a myosin gene enhancer element, as well as transactivation capacity, were abolished (Kerst et al., 2000). The patient inherited the MYF6 missense mutation from his more severely affected father, who was known to also have an in-frame DMD deletion mutation, but a more severe presentation than typical Becker muscular dystrophy (Kerst et al., 2000). The authors proposed that the two mutations resulted in a more severe phenotype than expected from either of the mutations individually.

CNM3 has been described in only one patient (Kerst et al. Neuromusc Disord 10:572-577, 2000), therefore, clinical and analytical sensitivity cannot yet be accurately estimated.

This test provides full coverage of all coding exons of the MYF6 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).