Insights from genotype-phenotype correlations by novel SPEG mutations causing centronuclear myopathy

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Centronuclear myopathies (CNM) are a group of congenital muscle disorders characterized by centrally located nuclei in muscle fibers.
• Myotubular myopathy, an X-linked form, is associated with mutations in the MTM1 gene and distinctive myotubular fibers.

Observation:

• Two unrelated patients presented with CNM and myotubular fibers on muscle biopsy.
• Next-generation sequencing identified novel biallelic homozygous mutations in the SPEG gene in both patients.
• Patient 1 had the c.1627_1628insA (p.Thr544Aspfs*48) mutation, while Patient 2 had the c.9586C>T (p.Arg3196*) mutation.

Findings:

• Patient 1 exhibited only myopathic features without cardiac involvement.
• Patient 2 developed dilated cardiomyopathy alongside milder myopathy.
• Whole-body muscle MRI was performed on Patient 2, revealing distinct phenotypes potentially linked to different SPEG isoforms.

Implications:

• These findings expand the known genotype-phenotype correlations for SPEG mutations.
• The study suggests that differential SPEG isoforms in skeletal muscle and heart may explain the variable clinical presentations.
• This research contributes to understanding the genetic basis and clinical spectrum of SPEG-associated myopathies.