X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is a dominantly inherited peripheral neuropathy and is caused by mutations in gap junction beta 1 gene (GJB1). Here, a novel variant of c.-170T>G in GJB1 was identified in a large Chinese CMTX1 pedigree. The proband presented transient “stroke-like” episodes in addition to the peripheral neuropathy. At the time of episode, he had transient hyperthyroidism. To our knowledge, this is the first variant found in non-coding region associated with transient central nervous system (CNS) symptoms and in this case, thyroid dysfunction might contribute to the episode. The mechanism of CMTX1 as well as the transient CNS symptoms waits to be elucidated.

Rationale: Autosomal dominant hypocalcaemia type 1 (ADH1) is a genetic disease characterized by benign hypocalcemia, inappropriately low parathyroid hormone levels and mostly hypercalciuria. It is caused by the activating mutations of the calcium-sensing receptor gene (CASR), which produces a left-shift in the set point for extracellular calcium. Patient concerns: A 50-year-old man presenting with muscle spasms was admitted into the hospital. He has a positive familial history for hypocalcemia. Auxiliary examinations demonstrated hypocalcemia, hyperphosphatemia, normal parathyroid hormone level and nephrolithiasis. A missense heterozygous variant in CASR, c 613C > T (p. Arg205Cys) which has been reported in a familial hypocalciuric hypercalcemia type 1 patient was found in the patient's genotype. It is the first time that this variant is found associating with ADH1. The variant is predicted vicious by softwares and cosegregates with ADH1 in this pedigree. CASR Arg205Cys was deduced to be the genetic cause of ADH1 in the family. Diagnosis: The patient was diagnosed with ADH1 clinically and genetically. Interventions: Oral calcitriol, calcium and hydrochlorothiazide were prescribed to the patient. Outcomes: After the treatments for 1 week, the patient's symptom was improved and the re-examination revealed serum calcium in the normal range. A 3-month follow-up showed his symptom was mostly relieved. Lessons: The variant of CASR Arg205Cys, responsible for ADH1 in this family, broadened the genetic spectrum of ADH1. Further and more studies are required to evaluate the correlation between genotype and phenotype in ADH1 patients.

Rationale: Limb-girdle muscular dystrophy (LGMD) is a genetic disease, which is characterized by muscle atrophy and weakness mainly involving proximal muscles. Accurate diagnosis of LGMD patient is very important for the appropriate management and long-term prognosis. Patient concerns: An 18-year-old woman presented with progressive weakness of limbs, persistent elevated serum creatine kinase, myogenic damages in electromyography, and dysferlin protein deficiency in muscle biopsy. Further next-generation sequencing (NGS) revealed a compound heterozygous variant in dysferlin gene (DYSF), including a novel frameshift variant of c.4010delT. Diagnosis: The patient was diagnosed with LGMD2B clinically and genetically. Interventions: Oral levocarnitine and coenzyme Q10 were prescribed to the patient. Outcomes: After symptomatic treatments for 1 week, the patient's symptoms were not improved. Lessons: NGS might be a helpful tool for the diagnosis of LGMD. A novel variant of c.4010delT in DYSF was identified in this case, which broadens the genetic spectrum of LGMD2B.

Objectives: By employing deep learning-based automatic whole-brain region segmentation technology, we aim to investigate the cross-sectional associations between regional brain volumes and disease duration in patients with Parkinson’s disease (PD). Methods: A retrospective study design was implemented on 83 patients diagnosed with idiopathic PD who had complete clinical and imaging data. Cranial magnetic resonance images (MRI) were imported into the uAI platform for automated regional segmentation of brain tissue. Volumetric data from five major brain regions and 80 subregions were extracted to explore their potential associations with disease progression in PD patients. Statistical analysis was conducted using a multiple linear regression model within the framework of linear regression analysis, with statistical significance defined as p < 0.05. Results: Cross-sectional analysis revealed that in PD patients, volume ratios of multiple brain regions—including the bilateral precentral gyrus, right medial frontal gyrus, bilateral postcentral gyrus, bilateral superior and inferior parietal lobules, bilateral precuneus, right cuneus, right lingual gyrus, bilateral lateral occipital gyrus, and right globus pallidus—were negatively associated with disease duration ( p < 0.05). In contrast, the right hippocampus, right inferior temporal gyrus, and left superior temporal gyrus showed positive correlations ( p < 0.05). The combined volume ratios of these brain regions also decreased with longer disease duration ( p < 0.05). Furthermore, absolute volume differences in the hippocampus, fusiform gyrus, isthmus of the cingulate gyrus, and cerebellar white matter increased as the disease progressed ( p < 0.05). Conclusion: In PD patients, volume ratios and absolute volume differences in specific brain subregions associated with lateralized intracranial changes may serve as potential biomarkers for assessing brain tissue alterations during disease progression.