Insights from genotype-phenotype correlations by novel SPEG mutations causing centronuclear myopathy.
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_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.
['Wang|Haicui|H|', 'Castiglioni|Claudia|C|', 'Kaçar Bayram|Ayşe|A|', 'Fattori|Fabiana|F|', 'Pekuz|Serdar|S|', 'Araneda|Diego|D|', 'Per|Hüseyin|H|', 'Erazo|Ricardo|R|', 'Gümüş|Hakan|H|', 'Zorludemir|Suzan|S|', 'Becker|Kerstin|K|', 'Ortega|Ximena|X|', 'Bevilacqua|Jorge Alfredo|JA|', 'Bertini|Enrico|E|', 'Cirak|Sebahattin|S|']
D002648:Child D002675:Child, Preschool D056726:Genetic Association Studies D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D009124:Muscle Proteins D018482:Muscle, Skeletal D009154:Mutation D020914:Myopathies, Structural, Congenital D010641:Phenotype D017346:Protein Serine-Threonine Kinases
SPEG Centronuclear myopathy Myotubular myopathy Exome Whole body MRI