Two novel deep intronic variants cause Duchenne muscular dystrophy by splice-altering mechanism.

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness, due to mutations in the DMD gene, which encodes the dystrophin protein. While mutations within the coding regions of DMD have been extensively studied, recent focus has shifted to deep intronic variants for their potential impact on disease severity. Here, we characterize two deep intronic variants, c.

Comprehensive analysis of 2097 patients with dystrophinopathy based on a database from 2011 to 2021.

Background: An increasing number of clinical trials for new therapeutic strategies are underway or being considered for dystrophinopathy. Having detailed data on the natural progression of this condition is crucial for assessing the effectiveness of new drugs. However, there's a lack of data regarding the long-term data on the natural course and how it's managed in China.

PIGW-related glycosylphosphatidylinositol deficiency: A case report and literature review.

Introduction: PIGW-related glycosylphosphatidylinositol deficiency is a rare disease that manifests heterogeneous clinical phenotypes.

Methods: We describe a patient with PIGW deficiency and summarize the clinical characteristics of the case. In addition, we conducted a literature review of previously reported patients with pathogenic variants of PIGW.

Spinal muscular atrophy with hypoplasia of the corpus callosum: a case report.

Background: Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder due to a defect in the survival motor neuron 1 (SMN1) gene. Hypoplasia of the corpus callosum is underdevelopment or thinness of the corpus callosum. SMA and callosal hypoplasia are relatively rare, and there is limited information sharing the diagnosis and treatment for SMA patients with callosal hypoplasia.

Comprehensive profile and natural history of pediatric patients with spinal muscular atrophy: A large retrospective study from China.

Background: There is a large population of people with spinal muscular atrophy (SMA) in China, and new disease-modifying therapies have become available recently. However, comprehensive data on the management and profile of treatment-naive SMA patients in China are still lacking.

Methods: As a retrospective study, a large cohort of treatment-naive patients with clinical and genetic diagnoses of 5q SMA were enrolled, ranging from neonatal to 18 years old, from the Neurology Department of Children's Hospital of Fudan University between January 2013 and December 2020.

Maternal secretin ameliorates obesity by promoting white adipose tissue browning in offspring.

Our knowledge of the coordination of intergenerational inheritance and offspring metabolic reprogramming by gastrointestinal endocrine factors is largely unknown. Here, we showed that secretin (SCT), a brain-gut peptide, is downregulated by overnutrition in pregnant mice and women. More importantly, genetic loss of SCT in the maternal gut results in undesirable phenotypes developed in offspring including enhanced high-fat diet (HFD)-induced obesity and attenuated browning of inguinal white adipose tissue (iWAT).

Phenotypes and genotypes of mitochondrial diseases with mtDNA variations in Chinese children: A multi-center study.

Mitochondrial DNA (mtDNA) associated mitochondrial diseases hold a crucial position but comprehensive and systematic studies are relatively rare. Among the 262 patients of four children's hospitals in China, 96%-point mutations (30 alleles in 11 genes encoding tRNA, rRNA, Complex I and V) and 4%-deletions (seven of ten had not been reported before) were identified as the cause of 14 phenotypes. MILS presented the highest genetic heterogeneity, while the m.

Myotonia Congenita: Clinical Characteristic and Mutation Spectrum of CLCN1 in Chinese Patients.

-related myotonia congenita (MC) is one of the most common forms of non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked contraction. However, there is limited data of clinical and molecular spectrum of MC patients in China. Five patients with myotonia congenita due to mutations in gene were enrolled, which were identified through trio-whole-exome sequencing or panel-based next-generation sequencing test.

Clinical and Genetic Characteristics of Mitochondrial Encephalopathy Due to Mutations: Two Chinese Case Reports and a Review of the Literature.

As one of the assembly factors of complex I in the mitochondrial respiratory chain, FOXRED1 plays an important role in mitochondrial function. However, only a few patients with mitochondrial encephalopathy due to FOXRED1 defects have been reported. Two Chinese patients with mitochondrial encephalopathy due to mutations in were identified through trio whole-exome sequencing.

Clinical Profile and Outcome of Pediatric Mitochondrial Myopathy in China.

Mitochondrial myopathy in children has notable clinical and genetic heterogeneity, but detailed data is lacking. In this study, we retrospectively reviewed the clinical presentation, laboratory investigation, genetic and histopathological characteristics, and follow-ups of 21 pediatric mitochondrial myopathy cases from China. Twenty-four patients suspected with mitochondrial myopathy were enrolled initially and 21 were genetically identified.

Gene therapeutic strategies and relevant clinical trials in neuromuscular disorder in China.

Neuromuscular disorder is a diverse group of genetic disease, among which Duchenne muscular dystrophy and Spinal muscular atrophy are most common. Recently, the great breakthroughs of gene targeted therapeutic strategies are leading a profound revolution in the standard care of neuromuscular disorders over the world including China. This review will offer an outline of the molecular pathogenesis, clinical progress, critical trials, as well as the challenges of new gene therapy in the treatment of Spinal muscular atrophy and Duchenne muscular dystrophy in China, mainly includes mRNA splicing modulators and adeno-associated virus mediated gene replacement.

Clinical and molecular characterization of pediatric mitochondrial disorders in south of China.

Mitochondrial disorders (MDs) are genetic ailments affecting all age groups. Epidemiological data and frequencies of gene mutations in pediatric patients in China are scarce. This retrospective study assessed 101 patients with suspected MDs treated at the Neurology Department of Children's Hospital, Fudan University, in 2011-2017.

Triazol: a privileged scaffold for proteolysis targeting chimeras.

Current traditional drugs such as enzyme inhibitors and receptor agonists/antagonists present inherent limitations due to occupancy-driven pharmacology as the mode of action. Proteolysis targeting chimeras (PROTACs) are composed of an E3 ligand, a connecting linker and a target protein ligand, and are an attractive approach to specifically knockdown-targeted proteins utilizing an event-driven mode of action. The length, hydrophilicity and rigidity of connecting linkers play important role in creating a successful PROTAC.

Concise synthesis of 2-methoxyestradiol from 17β-estradiol through the C(sp)-H hydroxylation.

A four-step route for the synthesis of 2-methoxyestradiol (5) starting from 17β-estradiol (1) has been achieved with a 51% overall yield. The key step was the ruthenium-catalyzed ortho-C(sp)-H bond hydroxylation of aryl carbamates. Using dimethyl carbamate as the directing group, [RuCl(p-cymene)] as the catalyst, PhI(OAc) as the oxidant and trifluoroacetate/trifluoroacetic anhydride (1:1) as the co-solvent, the hydroxyl group could be singly installed at the 2-position of 3-dimethylcarbamoyloxyestradiol (2) with 65% yield.

A comprehensive database of Duchenne and Becker muscular dystrophy patients (0-18 years old) in East China.

Background: Currently, there is no cure for Duchenne and Becker muscular dystrophies (DMD/BMD). However, clinical trials with new therapeutic strategies are being conducted or considered. A comprehensive database is critical for patient recruitment and efficacy evaluation.