Penetrance estimation of PRRT2 variants in paroxysmal kinesigenic dyskinesia and infantile convulsions.

Proline-rich transmembrane protein 2 (PRRT2) is the leading cause of paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), and infantile convulsions with choreoathetosis (ICCA). Reduced penetrance of PRRT2 has been observed in previous studies, whereas the exact penetrance has not been evaluated well. The objective of this study was to estimate the penetrance of PRRT2 and determine its influencing factors.

A novel frameshift ACTN2 variant causes a rare adult-onset distal myopathy with multi-minicores.

Introduction: Distal myopathies are a group of rare muscle disorders characterized by selective or predominant weakness in the feet and/or hands. In 2019, ACTN2 gene was firstly identified to be a cause of a new adult-onset distal muscular dystrophy calling actininopathy and another distinctly different myopathy, named multiple structured core disease (MsCD). Thus, the various phenotypes and limited mutations in ACTN2-related myopathy make the genotype-phenotype correlation hard to understand.

Clinical and genetic characteristics of Chinese patients with reducing body myopathy.

Reducing body myopathy (RBM) is a rare myopathy characterized by reducing bodies (RBs) in morphological presentation. The clinical manifestations of RBM present a wide clinical spectrum, varying from infantile lethal form through childhood and adult benign forms. FHL1 gene is the causative gene of RBM.

Bi-allelic loss of function variants in COX20 gene cause autosomal recessive sensory neuronopathy.

Sensory neuronopathies are a rare and distinct subgroup of peripheral neuropathies, characterized by degeneration of the dorsal root ganglia neurons. About 50% of sensory neuronopathies are idiopathic and genetic causes remain to be clarified. Through a combination of homozygosity mapping and whole exome sequencing, we linked an autosomal recessive sensory neuronopathy to pathogenic variants in the COX20 gene.

Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy.

Sorbitol dehydrogenase gene (SORD) has been identified as a novel causative gene of recessive forms of hereditary neuropathy, including Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy (dHMN). Our findings reveal two novel variants (c.404 A > G and c.

Identification and functional characterization of novel GDAP1 variants in Chinese patients with Charcot-Marie-Tooth disease.

Objective: To identify and characterize the pathogenicity of novel variants in Chinese patients with Charcot-Marie-Tooth disease.

Methods: Multiplex ligation-dependent probe amplification (MLPA) and whole-exome sequencing (WES) were performed in 30 unrelated CMT patients. Minigene assay was used to verify the effect of a novel splicing variant (c.

VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund's Adjuvant.

Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in modulating release of glutamate, acted a key player in the formation of heat hyperalgesia of inflammatory pain.

Presence of Multiple Autoimmune Antibodies Involved in Concurrent Myositis and Myocarditis and Myasthenia Gravis Without Thymoma: A Case Report.

Inflammatory myositis (IM) and myasthenia gravis (MG) are both immune disorders involving muscle. The concurrent presence of both conditions in the same patient is extremely rare and the diagnosis is important and challenging. Here, we report a case of concurrent myositis and myocarditis and MG without thymoma in a 69-year-old man with progressive proximal muscle weakness and dysphagia.

Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited sensorimotor neuropathies. To clarify the genetic spectrum and clinical profiles in Chinese CMT patients, we enrolled 150 unrelated CMT patients from southeast China. We performed multiplex ligation-dependent probe amplification (MLPA) testing in all patients and next-generation sequencing (NGS) among those patients without PMP22 rearrangements.

Functional study and pathogenicity classification of PRRT2 missense variants in PRRT2-related disorders.

Aims: PRRT2 variants are associated with various paroxysmal disorders. To date, more than 90 PRRT2 variants have been reported in PRRT2-related disorders. Lack of functional study in majority of missense variants makes their pathogenicity uncertain.

Associations between neuroanatomical abnormality and motor symptoms in paroxysmal kinesigenic dyskinesia.

Introduction: The pathophysiologic mechanism of paroxysmal kinesigenic dyskinesia (PKD) is largely unclear. Basal ganglia-thalamo-cortical circuit involvement is thought to underlie PKD pathophysiology. However, microstructural alternations in the motor circuit of PKD require further elucidation.

A Mutation in Dystrophin Causing Muscular Dystrophy in a Female Patient.

Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive neuromuscular diseases resulting from dystrophin (DMD) gene mutations. It has been known that the carrier of DMD mutations may also have symptoms of the disease. While de novo mutation is quite common in BMD/DMD patients, it is rarely reported in the female carriers.

Clinical features of familial amyloid polyneuropathy carrying transthyretin mutations in four Chinese kindreds.

Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is a rare hereditary disorder, characterized by a length-dependent polyneuropathy and dysfunction of various organs. Wide phenotypic heterogeneity makes early diagnosis difficult. In this study, we reviewed the clinical and electrophysiological features of four unrelated Chinese families with genetically confirmed TTR-FAP.

Mutation Analysis of MR-1, SLC2A1, and CLCN1 in 28 PRRT2-negative Paroxysmal Kinesigenic Dyskinesia Patients.

Background: Paroxysmal kinesigenic dyskinesia (PKD) is the most common subtype of paroxysmal dyskinesias and is caused by mutations in PRRT2 gene. The majority of familial PKD was identified to harbor PRRT2 mutations. However, over two-third of sporadic PKD patients did not carry anyPRRT2 mutation, suggesting an existence of additional genetic mutations or possible misdiagnosis due to clinical overlap.

Inositol-requiring protein 1α signaling pathway is activated in the temporal cortex of patients with mesial temporal lobe epilepsy.

Accumulating evidence suggests that repeated seizures could induce endoplasmic reticulum (ER) stress. Inositol-requiring protein 1α (IRE1α) is a vital pro-apoptotic molecule in ER stress, but it remains unclear whether the signaling pathway mediated by IRE1α is involved in human temporal lobe epilepsy. In this report, we investigated IRE1α-mediated ER stress pro-apoptotic signaling pathway in resected anterior temporal neocortex from 32 patients with intractable mesial temporal lobe epilepsy by immunofluorescence and western blot analysis.

Involvement of IRE1α signaling in the hippocampus in patients with mesial temporal lobe epilepsy.

Cumulative evidence suggests that programmed cell death (apoptosis) may contribute to the progressive hippocampal sclerosis seen in patients with refractory mesial temporal lobe epilepsy (MTLE). The endoplasmic reticulum (ER) stress-mediated cell apoptotic pathway has recently emerged as a vital intrinsic pathway, but the molecular mechanisms underlying this process in the epileptic brain remain unclear. We investigated inositol-requiring protein 1α (IRE1α)-mediated ER stress pro-and anti-apoptotic signaling pathways in resected hippocampi from 32 patients with intractable MTLE.

Reasonable neuropsychological battery to identify mild cognitive impairment.

Mild cognitive impairment (MCI) was popular studied while the neuropsychological tests to evaluate and identify MCI patients were not standard used. So there is a need to develop objective, cost-effective and normative screening tests which can evaluate cognitive problems for older individuals at risk of Alzheimer's disease (AD). According to lots of valuable research results, we hypothesize that a neuropsychological battery containing MMSE, AVLT, and MoCA could successfully identify MCI from other cognitive impairment.