Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2019 Mar;59(3):357-362.
doi: 10.1002/mus.26378. Epub 2018 Nov 28.

Novel SPEG mutations in congenital myopathies: Genotype-phenotype correlations

Anita E Qualls  1 , Sandra Donkervoort  2 , Johanna C Herkert  3 , Alissa M D'gama  1 , Diana Bharucha-Goebel  2   4 , James Collins  5 , Katherine R Chao  6 , A Reghan Foley  2 , Mirthe H Schoots  7 , Jan D H Jongbloed  3 , Carsten G Bönnemann  2 , Pankaj B Agrawal  1
Affiliations
Case Reports

Novel SPEG mutations in congenital myopathies: Genotype-phenotype correlations

Anita E Qualls et al. Muscle Nerve. 2019 Mar.

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 59:357-362, 2019.

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

PubMed Disclaimer

Conflict of interest statement

Disclosure of Conflicts of Interest: None of the authors has any conflict of interest to disclose.

Figures

Figure 1:
Figure 1:
Histological examination of patients’ muscle biopsies and SPEG schematic. (A) Hematoxylin & eosin (H&E) staining of Patient 1’s muscle biopsy specimen, performed at 9 years of age. The muscle biopsy shows a mild increase in fiber size variability, several atrophic fibers, and only a few internal/central nuclei, consistent with non-CNM CM. (B) SDH and (C) H&E staining of Patient 2’s muscle biopsy, performed at 3 years of age. The muscle biopsy reveals marked variability in fiber size with hypotrophic type 1 fibers and hypertrophic type II fibers with many central nuclei, consistent with CNM. Scale bar 50μm for all images. (D) Schematic of SPEGβ domain organization with positions of identified mutations generated by IBS (Illustrator for Biological Sequences). Mutations affecting both SPEGα and SPEGβ are in black, while mutations affecting only SPEGβ are in pink.
See this image and copyright information in PMC

References

    1. Nance JR, Dowling JJ, Gibbs EM, Bonnemann CG. Congenital myopathies: an update. Curr Neurol Neurosci Rep 2012;12(2):165–174. - PMC - PubMed
    1. Pierson CR, Tomczak K, Agrawal P, Moghadaszadeh B, Beggs AH. X-linked myotubular and centronuclear myopathies. J Neuropathol Exp Neurol 2005;64(7):555–564. - PubMed
    1. Bevilacqua JA, Monnier N, Bitoun M, Eymard B, Ferreiro A, Monges S, Lubieniecki F, Taratuto AL, Laquerriere A, Claeys KG, Marty I, Fardeau M, Guicheney P, Lunardi J, Romero NB. Recessive RYR1 mutations cause unusual congenital myopathy with prominent nuclear internalization and large areas of myofibrillar disorganization. Neuropathol Appl Neurobiol 2011;37(3):271–284. - PubMed
    1. Bitoun M, Maugenre S, Jeannet PY, Lacene E, Ferrer X, Laforet P, Martin JJ, Laporte J, Lochmuller H, Beggs AH, Fardeau M, Eymard B, Romero NB, Guicheney P. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet 2005;37(11):1207–1209. - PubMed
    1. Ceyhan-Birsoy O, Agrawal PB, Hidalgo C, Schmitz-Abe K, DeChene ET, Swanson LC, Soemedi R, Vasli N, Iannaccone ST, Shieh PB, Shur N, Dennison JM, Lawlor MW, Laporte J, Markianos K, Fairbrother WG, Granzier H, Beggs AH. Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy. Neurology 2013;81(14):1205–1214. - PMC - PubMed

Publication types