Novel SPEG variant cause centronuclear myopathy in China

Tang, Jia; Ma, Wei; Chen, Yangran; Jiang, Runze; Zeng, Qinlong; Tan, Jieliang; Jiang, Haihua; Li, Qing; Zhang, Victor W.; Wang, Jing; Tang, Hui; Luo, Lixia

doi:10.1002/jcla.23054

Cited by 12 publications

(12 citation statements)

References 27 publications

(52 reference statements)

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“…The reported SPEG gene variants are all related to CNM. A total of 16 variant sites have been reported including the two sites we discovered in our study as shown in Table 1 [10,[14][15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic analysis of a case with centronuclear myopathy caused by SPEG gene mutation: a case report and literature review

Zhang

Huang

et al. 2021

BMC Pediatr

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Background Centronuclear myopathy (CNM), a subtype of congenital myopathy (CM), is a group of clinical and genetically heterogeneous muscle disorders. Since the discovery of the SPEG gene and disease-causing variants, only a few additional patients have been reported. Case presentation The child, a 13-year-old female, had delayed motor development since childhood, weakness of both lower extremities for 10 years, gait swinging, and a positive Gower sign. Her distal muscle strength of both lower extremities was grade IV. The electromyography showed myogenic damage and electromyographic changes. Her 11-year-old sister had a similar muscle weakness phenotype. Gene sequencing revealed that both sisters had SPEG compound heterozygous mutations, and the mutation sites were c.3715 + 4C > T and c.3588delC, which were derived from their parents. These variant sites have not been reported before. The muscle biopsy showed the nucleic (> 20% of fibers) were located in the center of the cell, the average diameter of type I myofibers was slightly smaller than that of type II myofibers, and the pathology of type I myofibers was dominant, which agreed with the pathological changes of centronuclear myopathy. Conclusions The clinical phenotypes of CNM patients caused by mutations at different sites of the SPEG gene are also different. In this case, there was no cardiomyopathy. This study expanded the number of CNM cases and the mutation spectrum of the SPEG gene to provide references for prenatal diagnosis and genetic counseling.

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Section: Discussionmentioning

confidence: 99%

Clinical and genetic analysis of a case with centronuclear myopathy caused by SPEG gene mutation: a case report and literature review

Zhang

Huang

et al. 2021

BMC Pediatr

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“…Underlying these clinical phenotypes, cellular and molecular hallmarks of CNM include increased central nucleation of myofibers and variation in myofibers size, and disruptions in triadic structure and E-C coupling [ 10 , 44 , 45 ]. To date, 20 patients have been identified with SPEG mutations [ 23 , 44 , 46 , 47 , 48 , 49 ]. Figure 1 shows the location and mutation type of all reported SPEG variants.…”

Section: Speg Mutations In Myopathies and Cardiomyopathiesmentioning

confidence: 99%

“…Mutations affecting both SPEG isoforms are associated with more severe clinical and molecular phenotypes than those that spare SPEG α, the shorter isoform lacking amino acids 1-854 [ 8 ]. Of the eight patients shown to carry mutations affecting both SPEG α and SPEG β, all demonstrated cardiac dysfunction, five experienced early death, and one requires constant mechanical ventilation due to severe respiratory problems [ 8 , 43 , 44 , 46 , 51 ]. Mutations affecting only SPEG β are associated with a milder phenotype without cardiac involvement [ 43 , 44 , 50 ], indicating that SPEGα is critical for both skeletal and cardiac function and may be able to partially compensate for SPEGβ loss-of-function.…”

Section: Speg Mutations In Myopathies and Cardiomyopathiesmentioning

confidence: 99%

Striated Preferentially Expressed Protein Kinase (SPEG) in Muscle Development, Function, and Disease

Luo

Rosen

et al. 2021

IJMS

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Mutations in striated preferentially expressed protein kinase (SPEG), a member of the myosin light chain kinase protein family, are associated with centronuclear myopathy (CNM), cardiomyopathy, or a combination of both. Burgeoning evidence suggests that SPEG plays critical roles in the development, maintenance, and function of skeletal and cardiac muscles. Here we review the genotype-phenotype relationships and the molecular mechanisms of SPEG-related diseases. This review will focus on the progress made toward characterizing SPEG and its interacting partners, and its multifaceted functions in muscle regeneration, triad development and maintenance, and excitation-contraction coupling. We will also discuss future directions that are yet to be investigated including understanding of its tissue-specific roles, finding additional interacting proteins and their relationships. Understanding the basic mechanisms by which SPEG regulates muscle development and function will provide critical insights into these essential processes and help identify therapeutic targets in SPEG-related disorders.

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“…Mutations in genes such as MTM1, DNM2, BIN1, RYR1, CACNA1S, and TTN have been identified for about 60-80% of patients with CNM. In recent studies, the mutations in the SPEG gene (striated muscle preferentially expressed protein kinase) have been associated with CNM in a small case series (3)(4)(5)(6)(7). Herein, we report a case of CM due to a novel variation in the SPEG gene, which is manifested by intellectual disability, a new clinical finding.…”

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confidence: 90%

Mild congenital myopathy due to a novel variation in <i>SPEG </i>gene

Yıldırım

Balasar

Köse

et al. 2021

IRDR

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congenital myopathy, striated muscle preferentially expressed protein kinase, SPEG, centronuclear myopathy, intellectual disability Centronuclear myopathies (CNMs) are a subgroup of congenital myopathies (CMs) characterized by muscle weakness, genetic heterogeneity, and predominant type 1 fibers and increased central nuclei in muscle biopsy. Mutations in CNM-causing genes such as MTM1, DNM2, BIN1, RYR1, CACNA1S, TTN, and extraordinary rarely SPEG (striated muscle preferentially expressed protein kinase) have been identified for about 60-80% of patients. Herein, we report a case of CM due to a novel variation in the SPEG gene, manifested by mild neonatal hypotonia, muscle weakness, delayed motor milestones, and ophthalmoplegia, without dilated cardiomyopathy. We identified a novel variation [c.153C>T (p.Asn51=) in exon 1] in the SPEG gene with whole-exome sequencing and confirmed by Sanger sequencing. Mild intellectual disability has not been associated with SPEG-related CM in the previous reports. We suggest that this report expands the phenotypic spectrum of SPEG-related CM, and further case reports are required to expand the genotype-phenotype correlations.

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Novel SPEG variant cause centronuclear myopathy in China

Cited by 12 publications

References 27 publications

Clinical and genetic analysis of a case with centronuclear myopathy caused by SPEG gene mutation: a case report and literature review

Clinical and genetic analysis of a case with centronuclear myopathy caused by SPEG gene mutation: a case report and literature review

Striated Preferentially Expressed Protein Kinase (SPEG) in Muscle Development, Function, and Disease

Mild congenital myopathy due to a novel variation in <i>SPEG </i>gene

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