シャルコー・マリー・トゥース病

Aminoacyl-tRNA synthetases (ARSs) are a family of enzymes that attach amino acids to tRNAs. To date, all 37 human ARS genes have been implicated in genetic diseases, affecting over a thousand patients worldwide. At the 2025 Federation of European Biochemical Societies (FEBS) Special Meeting 'Expanding Frontiers in Aminoacyl-tRNA Synthetase Research', patients, families, and advocacy groups communicated the need for a unified approach for reporting on ARS gene names and associated conditions in the scientific literature. This request stemmed from the current use of multiple nomenclature systems and the desire of these individuals to rapidly identify published data on specific ARS genes. Here, we summarize ARS gene nomenclature and request that the scientific community adhere to a single nomenclature system.

Proteins with intrinsically disordered regions (IDRs) perform essential cellular functions despite lacking stable structures, challenging the traditional structure-function paradigm. Neurofilament-light (NFL) proteins self-assemble into bottlebrush filaments, whose disordered tail domains mediate nematic hydrogel formation critical for neuronal integrity. Mutations in NFL are linked to Charcot-Marie-Tooth (CMT) disease, yet their molecular effects remain unclear. Here, aiming to gain insight into these molecular mechanisms, we combine small-angle X-ray scattering, microscopy, and deep-learning conformational analysis to investigate CMT-associated NFL tail mutations. We find that these mutations compact the hydrogel, disrupt filament nematic order by generating microdomains, and alter water retention dynamics by shifting sequence-dependent conformational ensembles, leading to macroscopic network rearrangements. These findings demonstrate how subtle sequence changes in IDRs modulate protein network organization and function, offering structural insights into IDR-related pathologies.

Charcot-Marie-Tooth syndrome type X1 (CMTX1) is an inherited motor and sensory neuropathy caused by mutations in the GJB1 gene located in the X chromosome. Although uncommon, stroke-like episodes have been reported in patients with CMTX1, typically triggered by stress and characterized by distinctive magnetic resonance imaging findings with complete spontaneous resolution. We report the case of a 13-year-old boy with CMTX1 and no prior neurological symptoms who developed right hemiparesis, dysarthria, and facial deviation following a wasp sting. After activation of the stroke code, brain magnetic resonance revealed bilateral hyperintense lesions in the centrum semiovale without evidence of thrombosis. To our knowledge, this is the first paediatric case of CMTX1 in which an insect sting acted as a trigger, mimicking stroke. Prompt activation of stroke protocols and neuroimaging is essential to establish the diagnosis and exclude other conditions.

BACKGROUND: X-linked Charcot-Marie-Tooth disease type 1 (CMTX1), caused by pathogenic variants in GJB1 encoding connexin 32, is primarily an inherited peripheral neuropathy. A minority of patients develop transient central nervous system (CNS) dysfunction with reversible white matter lesions, which may mimic acute paediatric stroke. Triggers such as fever, infection and exercise have been reported, but allergy-related exposure has rarely been discussed and causal mechanisms remain uncertain. CASE PRESENTATION: A 9-year-old boy developed acute left-sided weakness, dysarthria and central facial-tongue paresis shortly after pollen exposure. Cranial magnetic resonance imaging (MRI) showed symmetrical diffusion-restricted lesions involving the corpus callosum and bilateral centrum semiovale, with high signal on diffusion-weighted imaging (DWI), corresponding low apparent diffusion coefficient (ADC) values and hyperintensity on T2 fluid-attenuated inversion recovery (FLAIR). Magnetic resonance angiography (MRA), magnetic resonance venography (MRV), cerebrospinal fluid (CSF) studies, autoimmune encephalitis antibodies and oligoclonal bands were unremarkable. Neurological deficits resolved within 12 h. Nerve conduction studies showed mild mixed sensorimotor polyneuropathy with demyelinating features and partial axonal involvement. Serial MRI showed progressive resolution, and diffusion tensor imaging (DTI) demonstrated no obvious displacement, interruption or reduction of major white matter tracts. Whole-exome sequencing and Sanger validation identified a hemizygous GJB1 c.623 A > G (p.Glu208Gly, p.E208G) variant in the proband; his mother was heterozygous and his brother was hemizygous. No recurrent stroke-like episode occurred during 2 years of follow-up, although reduced tendon reflexes persisted. CONCLUSIONS: In children with acute stroke-like episodes and reversible white matter lesions, the coexistence of pes cavus, reduced tendon reflexes or abnormal nerve conduction should prompt evaluation for GJB1-related CMTX1. Pollen exposure was temporally associated with the episode in this patient, but an allergic mechanism remains unproven because allergy-specific biomarkers and cytokines were not obtained during the acute phase.

BACKGROUND AND AIMS: Hereditary neuropathies are a group of genetically and phenotypically heterogeneous neuropathies. These are classified into: hereditary sensory motor neuropathy (HSMN) aka Charcot-Marie-Tooth disease (CMT), distal motor neuropathy (dMN), hereditary sensory autonomic neuropathy (HSAN), episodic neuropathies and polyneuropathy as part of a complex clinical presentation. The aim of this study was to determine final diagnoses in patients referred from the tertiary center in Serbia under suspicion of hereditary neuropathy. METHODS AND MATERIALS: This research included 340 patients directed for genetic testing from the Neurology Clinic, University Clinical Center of Serbia during the period from 2009 to 2023, who underwent complete genetic analyses available. RESULTS: The most prominent demyelinating neuropathy was group consisted of patients with CMT1A (93 (27.3%)), followed by CMT1B (10 (2.9%)). In the group of patients with axonal form of the disease, the most prevalent was the one with pathogenic variant in HINT1 (18 (5.3%)). Nineteen (5.6%) patients have had variants in GJB1 gene. DMN group was composed of seven (2%) patients. HSAN was final diagnosis in 2 (0.6%) patients. Group of 16 (4.7%) patients have had neuropathy as part of a complex clinical presentation. In 70 (20.6%) patients no significant genetic variant was found, even though clinical presentation was highly suggestive of hereditary neuropathy. INTERPRETATION: In line with other populations, CMT1A was the most common cause of hereditary neuropathy in Serbia. The axonal cohort predominantly included patients with variants in the HINT1 gene, which represents a population-specific characteristic. These findings highlight the importance of targeted genetic analysis in diagnosing hereditary neuropathies in certain populations.