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Muscle Nerve. 2018 Nov 9. doi: 10.1002/mus.26378. [Epub ahead of print]

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

Author information

1
Division of Newborn Medicine, Division of Genetics and Genomics, and The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA.
2
Neuromuscular and Neurogenetic Disorders of Childhood, National Institutes of Health, Bethesda, Maryland, USA.
3
University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, the Netherlands.
4
Division of Neurology, Children's National Health System, Washington, DC, USA.
5
Mercy Clinic Pediatric Neurology, Springfield, Missouri, USA.
6
Center for Mendelian Genomics at the Broad Institute of MIT and Harvard, Boston, Massachusetts, USA.
7
Department of Pathology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.

Abstract

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, 2018.

KEYWORDS:

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

PMID:
30412272
DOI:
10.1002/mus.26378

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