Novel SPEG mutations in congenital myopathies: Genotype-phenotype correlations.

TitleNovel SPEG mutations in congenital myopathies: Genotype-phenotype correlations.
Publication TypeJournal Article
Year of Publication2019
AuthorsQualls, AE, Donkervoort, S, Herkert, JC, D'Gama, AM, Bharucha-Goebel, D, Collins, J, Chao, KR, A Foley, R, Schoots, MH, Jongbloed, JDH, Bönnemann, CG, Agrawal, PB
JournalMuscle Nerve
Date Published2019 03
KeywordsBiopsy, Child, Child, Preschool, Consanguinity, Exome, Female, Genetic Association Studies, Humans, Infant, Male, Muscle Proteins, Muscle Weakness, Muscle, Skeletal, Mutation, Myopathies, Structural, Congenital, Protein-Serine-Threonine Kinases, Sequence Analysis

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.

Alternate JournalMuscle Nerve
PubMed ID30412272
Grant ListR01 AR068429 / AR / NIAMS NIH HHS / United States
UM1 HG008900 / HG / NHGRI NIH HHS / United States