Back to Search
Start Over
Insights from genotype-phenotype correlations by novel SPEG mutations causing centronuclear myopathy.
- Source :
-
Neuromuscular disorders : NMD [Neuromuscul Disord] 2017 Sep; Vol. 27 (9), pp. 836-842. Date of Electronic Publication: 2017 May 24. - Publication Year :
- 2017
-
Abstract
- Centronuclear myopathies (CNM) are a clinically and genetically heterogeneous group of congenital myopathies, defined histologically by increased number of fibres with centrally located nuclei, and type I fibre predominance in muscle biopsy. Myotubular myopathy, the X-linked form of CNM caused by mutations in the phosphoinositide phosphatase MTM1, is histologically characteristic since muscle fibres resemble myotubes. Here we present two unrelated patients with CNM and typical myotubular fibres in the muscle biopsy caused by mutations in striated muscle preferentially expressed protein kinase (SPEG). Next generation sequencing revealed novel biallelic homozygous mutations in SPEG in both cases. Patient 1 showed the c.1627&#95;1628insA (p.Thr544Aspfs*48) mutation and patient 2 the c.9586C>T (p.Arg3196*) mutation. The clinical phenotype was distinctive in the two patients since patient 2 developed a dilated cardiomyopathy with milder myopathy features, while patient 1 showed only myopathic features without cardiac involvement. These findings expand the genotype-phenotype correlations after the initial report. Additionally, we describe whole body muscle MRI of patient 2 and we argue on the different SPEG isoforms in skeletal muscle and heart as the possible explanation leading to variable phenotypes of SPEG mutations.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Child
Child, Preschool
Humans
Magnetic Resonance Imaging
Male
Muscle, Skeletal diagnostic imaging
Muscle, Skeletal physiopathology
Myopathies, Structural, Congenital diagnostic imaging
Myopathies, Structural, Congenital pathology
Phenotype
Genetic Association Studies
Muscle Proteins genetics
Mutation genetics
Myopathies, Structural, Congenital etiology
Myopathies, Structural, Congenital genetics
Protein Serine-Threonine Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2364
- Volume :
- 27
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Neuromuscular disorders : NMD
- Publication Type :
- Academic Journal
- Accession number :
- 28624463
- Full Text :
- https://doi.org/10.1016/j.nmd.2017.05.014