Insights from genotype–phenotype correlations by novel SPEG mutations causing centronuclear myopathy

Wang, Haicui; Castiglioni, Claudia; Bayram, Ayşe Kaçar; Fattori, Fabiana; Pekuz, Serdar; Araneda, Diego; Per, Hüseyin; Erazo, Ricardo; Gümüş, Hakan; Zorludemir, Suzan; Becker, Kerstin; Ortega, Ximena; Bevilacqua, Jorge A.; Bertini, Enrico; Çırak, Sebahattin

doi:10.1016/j.nmd.2017.05.014

Cited by 26 publications

(31 citation statements)

References 13 publications

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“…Approximately 60–80% of CNMs are caused by dominant DNM2 mutations, dominant and recessive RYR1 and CACNA1S mutations, recessive BIN1 mutations, and X‐linked recessive MTM1 mutations . Recently, recessive SPEG mutations have been identified in 6 CNM patients and 1 patient with non‐CNM CM . Here, we report 2 additional unrelated patients with CMs caused by recessive SPEG mutations, compare the clinical findings of all 9 patients, and discuss genotype–phenotype correlations thereby improving the understanding of SPEG ‐related CM.…”

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confidence: 91%

Novel SPEG mutations in congenital myopathies: Genotype–phenotype correlations

et al. 2018

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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

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confidence: 91%

Novel SPEG mutations in congenital myopathies: Genotype–phenotype correlations

et al. 2018

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“…Clinical data from Patients 4, 8, and 10 suggest that SPEGα may partially rescue mutations affecting only SPEGβ, possibly preserving cardiac function. SPEGα and SPEGβ are proteins within the junctional membrane complex (JMCs) that reported to regulatory junctophilin‐2 (JPH2) phosphorylation, which is a key role for transverse tubules maintenance in cardiac myocytes . Clinical data from patients carried mutation affecting SPEGα and SPEGβ.…”

Section: Discussionmentioning

confidence: 99%

“…SPEGα and SPEGβ are proteins within the junctional membrane complex (JMCs) that reported to regulatory junctophilin-2 (JPH2) phosphorylation, which is a key role for transverse tubules maintenance in cardiac myocytes. 16 Clinical data from patients 3,[5][6][7]9,11 carried mutation affecting SPEGα and SPEGβ. These findings suggest the disease is more severe when both isoforms are affected.…”

Section: Discussionmentioning

confidence: 99%

“…Recessive SPEG (Striated muscle enriched protein kinase) mutations were first identified in CNM patients by Agrawal in 2014 . To date, SPEG mutations have been identified in eight CNM and 1 CM patients . Most of these patients had severe hypotonia and muscle weakness.…”

Section: Introductionmentioning

confidence: 99%

“…13 To date, SPEG mutations have been identified in eight CNM and 1 CM patients. [13][14][15][16][17] Most of these patients had severe hypotonia and muscle weakness.…”

Section: Introductionmentioning

confidence: 99%

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Novel SPEG variant cause centronuclear myopathy in China

Tang

Chen³

et al. 2019

Clinical Laboratory Analysis

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Background Centronuclear myopathy (CNM), a subtype of congenital myopathy (CM), is a group of clinical and genetically heterogeneous muscle disorders. Centronuclear myopathy is a kind of disease difficult to diagnose due to its genetic diversity. Since the discovery of the SPEG gene and disease‐causing variants, only a few additional patients have been reported. Methods A radiograph test, ultrasonic test, and biochemical tests were applied to clinical diagnosis of CNM. We performed trio medical exome sequencing of the family and conservation analysis to identify variants. Results We report a pair of severe CNM twins with the same novel homozygous SPEG variant c. 8710A>G (p.Thr2904Ala) identified by clinical trio medical exome sequencing of the family and conservation analysis. The twins showed clinical symptoms of facial weakness, hypotonia, arthrogryposis, strephenopodia, patent ductus arteriosus, and pulmonary arterial hypertension. Conclusions Our report expands the clinical and molecular repertoire of CNM and enriches the variant spectrum of the SPEG gene in the Chinese population and helps us further understand the pathogenesis of CNM.

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