ABSTRACT
Charcot-Marie-Tooth diseases are a group of most common inherited peripheral neuropathies. The predominant clinical presentations include distal predominance of limb-muscle weakness and atrophy, and sensory loss, as well as skeletal deformities such as pes cavus and scoliosis. On the basis of electrophysiological studies, nerve pathology, and inheritance characteristics, Charcot-Marie-Tooth diseases are subdivided into several types. Genetic tests are helpful to identify the pathogenic genes. Rehabilitation, surgical treatment, and symptomatic drug therapy contribute to ameliorate symptoms and skeletal deformities. Some specific therapeutic drugs targeting pathogenesis have been tested in clinical trials, though their efficacy and safety require further investigation.
ABSTRACT
Neurogenetic diseases are a group of hereditary diseases that predominantly affect the nervous system, including the central nervous system, peripheral nerves, and muscles. The clinical manifestations are complex, and the treatments are rather difficult. In recent years, with the in-depth study of the etiology and pathogenesis of neurogenetic diseases, gene therapeutic approaches developed for mutant genes, such as antisense oligonucleotides, RNA interference, adeno-associated virus-mediated gene transduction, small molecule compounds with gene modification effects, and clustered regularly interspaced short palindromic repeats/Cas9 gene editing strategies are gradually transformed into clinical applications. The drugs with potential therapeutic effects are developed in according to the promising targets within the pathogenic mechanism of diseases. These emerging therapeutic approaches provide innovative prospects for patients with neurogenetic diseases.
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Objective To investigate the clinical and electrophysiological features of patients with non-inflammatory myopathy with neurogenic lesions. Method The clinical and electromyography data was retrospectively collected from 110 patients who were diagnosed with myopathy and completed routine electromyography examination from 2015 to 2017. A retrospective analysis of clinical and electrophysiological features was conducted on 4 patients with non-inflammatory myopathy with neurogenic lesions. Result Of the 110 patients, 10 patients with neurogenic lesions and 4 of them were diagnosed to have non-inflammatory myopathy. These 4 patients had limb and trunk weakness with muscle atrophy and the electromyography showed neurogenic lesion with or without peripheral nerve lesion. Conclusion This study has revealed neurogenic lesions in a small number of non-inflammatory myopathy on the electromyography, suggesting that the electromyography alone may not be sufficient for diagnosis of myopathy.
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<p><b>OBJECTIVE</b>To explore the significance of SMN1 gene mutations among patients with spinal muscular atrophy (SMA) and the value of multiplex ligation dependent probe amplification (MLPA) for its diagnosis.</p><p><b>METHODS</b>Potential mutations of the SMN1 gene were detected among 78 SMA patients with a MLPA assay.</p><p><b>RESULTS</b>Homozygous deletion of SMN1 exons 7 and 8 was detected in 70 (89.7%) of all patients. Homozygous deletion of exons 7 and heterozygous deletion of exon 8 was detected in 3 patients (3.8%). Homozygous deletion of SMN1 exons 7 alone was detected in 3 patients (3.8%). Heterozygous deletion of SMN1 exons 7 and 8 was detected in 2 patients (2.6%). For 77 of the patients, both parents were found to carry heterozygous deletion of the SMN1 gene, which was consistent with the recessive inheritance of SMA. One patient with SMA type I was found to be rather rare. The patient was found to carry homozygous deletion of SMN1 exons 7 and 8, for which her mother was heterozygous, while no mutation was found in her father.</p><p><b>CONCLUSION</b>Homozygous deletion of the SMN1 gene have been detected in more than 95% of SMA patients. No homozygous deletion of exon 8 has been found. Homozygous deletion of exon 7 is more significant in the pathogenesis of SMA.</p>
Subject(s)
Female , Humans , Male , Exons , Gene Deletion , Multiplex Polymerase Chain Reaction , Muscular Atrophy, Spinal , Genetics , Mutation , Survival of Motor Neuron 1 Protein , GeneticsABSTRACT
[Objective] To explore the clinical features,genetic characters in family amyotrophic lateral sclerosis (ALS10)patients.[Methods] TARDBP gene mutations in Chinese Han family patients with ALS10 diagnosed by the First Affiliated Hospital of Sun Yat-sen University in 2013 was screened by high-throughput sequencing.[Results] There were 5 patients in three generations in this family.The initial symptoms in all affected members were distal limb muscle weakness and dystrophy at their 50 age.With a rapid progression of symptoms about 8 to 18 months.A homozygous missense mutation (c.892G>A) were detected in TARDBP gene exon 6 of the propositus,as well as the other three family members without any clinical symptoms.[Conclusion] ALS10 is a faster progressive and shorter survival time FALS.Since there was no effective treatment in ALS10,hereditary consultation and prenatal diagnosis play an important role in disease prevention and hereditary.
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Objective To analyze the clinical features of 35 cases of Kennedy's disease and the correlation be?tween clinical features and CAG repeat size to strengthen the understanding of KD and to avoid misdiagnosis and delayed diagnosis.Methods Clinical data, including clinical signs and symptoms ,serum lipid, serum sex hormone level, electro?myography, the number of CAGs and (amyotrophic lateral sclerosis muscular atrophy,ALS) rating scale were collected from 35 patients genetically diagnosed of Kennedy disease and proceed system analysis. Results Patients with KD were adult onset with the average age of (40.77 ± 8.57) years and the average confirmed course were (8.32 ± 4.17) years. Forty-two point nine percent of the patients had family history. Clinical features included medulla oblongata and spinal muscular atrophy and weakness, limbs tremor, perioral muscles twitch and endocrine function and metabolic disorders in some cases. Creatine kinase, triglyceride, low density lipoprotein, follicle estrogen and prolactin were significantly in?creased compared to healthy adults (P:0.000,0.018,0.000,0.000,0.003). The number of CAG repeat was negatively correlated with the onset age (r=-0.549, P=0.001) but not associated with the illness severity (ALS rating scale) (r=0.001, P=0.998). ALS score was negatively correlated with course of disease(r=-0.540, P=0.001).Conclusions Chinese KD pa? tients share similar clinical phenotypes with those of other races but exhibit slightly different clinical characteristics. The length of the CAG repeat influences age at onset but not the severity of disease. Severity of disease is related to the course of disease.
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Objective To describe the clinical features, differential diagnosis and therapeutic method of Madras motor neuron disease (MMND) to improve the understanding of MMND. Methods We retrospectively summarized the clinical data of 3 MMND patients. and conducted the related literature review to compare the similarities and differences on clinical features between our cases and foreign MMND patients. Results Patients in the present study were adult-on?set without definite family history. The main manifestations were multiple lower cranial nerve palsies along with weakness and wasting of proximal limbs. Bifacial palsy and dysarthria were most presented in patients, while definite hearing im?pairment was rarely seen. Two patients had fasciculation and atrophy in tongue and one presented with dysphagia. Weak?ness and atrophy were more frequently presented in upper extremities than in lower limbs. All patients had signs of upper motor neuron damage. The level of creatine kinase (CK) moderately increased in one case. Electromyography (EMG) de?tected a widespread neuronal damage in all patients. MMND should be differentiated from Amyotrophic Lateral Sclerosis, Kennedy Disease and Brown–Vialetto–van Laere Syndrome. Intravenous immunoglobulin therapy showed effective in some cases to some extent. Compare to foreign MMND patients, bifacial weakness at onset was more frequently presented in our patients, but hearing impairment was absent. Conclusion The clinical features of MMND include weakness and at?rophy of limbs, involvement of facial and bulbar muscles, pyramidal dysfunction and hearing impairment. Some clinical manifestations of our patients are different from foreign MMND patient.