Novel SPEG mutations in congenital myopathies: Genotype-phenotype correlations

Muscle Nerve. 2019 Mar;59(3):357-362. doi: 10.1002/mus.26378. Epub 2018 Nov 28.


Introduction: Centronuclear myopathies (CNMs) are a subtype of congenital myopathies (CMs) characterized by muscle weakness, predominant type 1 fibers, and increased central nuclei. SPEG (striated preferentially expressed protein kinase) mutations have recently been identified in 7 CM patients (6 with CNMs). We report 2 additional patients with SPEG mutations expanding the phenotype and evaluate genotype-phenotype correlations associated with SPEG mutations.

Methods: Using whole exome/genome sequencing in CM families, we identified novel recessive SPEG mutations in 2 patients.

Results: Patient 1, with severe muscle weakness requiring respiratory support, dilated cardiomyopathy, ophthalmoplegia, and findings of nonspecific CM on muscle biopsy carried a homozygous SPEG mutation (p.Val3062del). Patient 2, with milder muscle weakness, ophthalmoplegia, and CNM carried compound heterozygous mutations (p.Leu728Argfs*82) and (p.Val2997Glyfs*52).

Conclusions: The 2 patients add insight into genotype-phenotype correlations of SPEG-associated CMs. Clinicians should consider evaluating a CM patient for SPEG mutations even in the absence of CNM features. Muscle Nerve 59:357-362, 2019.

Keywords: cardiomyopathy; centronuclear myopathies; congenital myopathies; myotubularin (MTM1); next generation sequencing (NGS); striated preferentially expressed protein kinase (SPEG).

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Biopsy
  • Child
  • Child, Preschool
  • Consanguinity
  • Exome / genetics
  • Female
  • Genetic Association Studies
  • Humans
  • Infant
  • Male
  • Muscle Proteins / genetics*
  • Muscle Weakness / etiology
  • Muscle Weakness / genetics
  • Muscle, Skeletal / pathology
  • Mutation / genetics
  • Myopathies, Structural, Congenital / congenital*
  • Myopathies, Structural, Congenital / genetics*
  • Protein-Serine-Threonine Kinases / genetics*
  • Sequence Analysis


  • Muscle Proteins
  • Protein-Serine-Threonine Kinases
  • SPEG protein, human