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.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid, and choline metabolism caused by mutations in EFTA, EFTB, or ETFDH. Many MADD patients are responsive to treatment with riboflavin, termed riboflavin-responsive MADD (RR-MADD). Here, we report three novel mutations and one previously reported mutation in ETFDH in four RR-MADD patients who presented at various ages, and characterize the corresponding changes in ETF-QO protein structure. Clinicians should consider MADD in the differential diagnosis when patients present with muscle weakness and biochemical abnormalities. Gene testing plays a critical role in confirming the diagnosis of MADD, and may not only prevent patients from invasive testing, but also allow timely initiation of riboflavin treatment. The novel variants in ETFDH and the corresponding clinical features reported here enrich the allelic heterogeneity of RR-MADD and provide insight into genotype-phenotype relationships.

Human bocavirus-1 (HBoV1) is an emerging viral pathogen associated with acute respiratory tract infections (ARTIs) in pediatric populations. This study aimed to evaluate the infection status and clinical characteristics of HBoV1 among hospitalized children suffering from ARTIs. A cohort of 5,021 pediatric patients with respiratory infections was analyzed using targeted next-generation sequencing to identify HBoV1 and other co-existing respiratory pathogens. Results indicated a detection rate of HBoV1 of 8.48%, predominantly among infants under 24 months, with a higher prevalence observed in males. Among the 426 children with HBoV1 detected, there were 17 cases (4%) of single HBoV1 infection, and 409 cases (96%) were co-infected with HBoV1 and other pathogens. The predominant infection pattern was HBoV1-bacteria-virus co-infection (155 cases). A total of 48 other pathogens were detected in children with HBoV1 co-infections, with rhinovirus and human herpesvirus being the most common. The median hospitalization duration for the children with HBoV1 was 8 days, and 16.26% required ICU admission for monitoring. The study offers a comprehensive analysis of the distribution of co-infecting pathogens, clinical features, and outcomes in hospitalized children with HBoV one infection. IMPORTANCE: There is currently a poor understanding of the characteristics and clinical manifestations of human bocavirus-1 (HBoV1) infection. In the past decade, few studies have thoroughly analyzed co-infecting pathogens, such as viruses, bacteria, and fungi and their patterns in relation to HBoV1. This study utilizes targeted next-generation sequencing (tNGS) technology to identify HBoV1 and other common respiratory pathogens in 5,021 hospitalized children suffering from respiratory infections in the Guangxi region. It offers a detailed analysis of the distribution of co-infecting pathogens, infection patterns, laboratory findings, clinical manifestations, imaging features, complications, and prognoses related to HBoV1 infection in this population. The study highlights the high co-infection rates associated with HBoV1 and offers important insights for diagnosing, treating, and managing children with HBoV1 infection.

Striated preferentially expressed gene (SPEG), a member of the myosin light chain kinase family, is localized at the level of triad surrounding myofibrils in skeletal muscles. In humans, SPEG mutations are associated with centronuclear myopathy and cardiomyopathy. Using a striated muscle-specific Speg-knockout (KO) mouse model, we have previously shown that SPEG is critical for triad maintenance and calcium handling. Here, we further examined the molecular function of SPEG and characterized the effects of SPEG deficiency on triad and focal adhesion proteins. We used yeast two-hybrid assay, and identified desmin, an intermediate filament protein, to interact with SPEG and confirmed this interaction by co-immunoprecipitation. Using domain-mapping assay, we defined that Ig-like and fibronectin III domains of SPEG interact with rod domain of desmin. In skeletal muscles, SPEG depletion leads to desmin aggregates in vivo and a shift in desmin equilibrium from soluble to insoluble fraction. We also profiled the expression and localization of triadic proteins in Speg-KO mice using western blot and immunofluorescence. The amount of RyR1 and triadin were markedly reduced, whereas DHPRα1, SERCA1 and triadin were abnormally accumulated in discrete areas of Speg-KO myofibers. In addition, Speg-KO muscles exhibited internalized vinculin and β1 integrin, both of which are critical components of the focal adhesion complex. Further, β1 integrin was abnormally accumulated in early endosomes of Speg-KO myofibers. These results demonstrate that SPEG-deficient skeletal muscles exhibit several pathological features similar to those seen in MTM1 deficiency. Defects of shared cellular pathways may underlie these structural and functional abnormalities in both types of diseases.