Background: Anti-GQ1b antibody syndrome referred to a clinical spectrum characterized by acute onset of ataxia, ophthalmoplegia and areflexia, while visual deterioration was rarely reported in terms of ocular disorders. This study aimed to describe the clinical characteristics of anti-GQ1b antibody syndrome with visual impairment. Methods: The database at the First Affiliated Hospital of Sun Yat-sen University was searched from 2014 to 2020. Patients with anti-GQ1b IgG were identified and divided into two groups according to the existence of optic neuropathy. Clinical and laboratory data of these subjects between the two groups were collected and analyzed. All patients were followed up by telephone to assess the outcome. Results: A total of 12 patients with seropositive anti-GQ1b antibody were included, 75% of which got antecedent infection. Of these cases, 3 showed visual deterioration accompanied by abnormal orbital magnetic resonance imaging or visual evoked potentials, and the other 9 didn't show any evidence of vision impairment. Patients in the optic neuropathy group presented prominent visual impairments as initial symptoms and were more likely to suffer from facial weakness. There were 4 patients in normal visual acuity group complaining of blurred vision due to intraocular muscle paralysis, which was distinguished by subsequent examination. The combination of glucocorticoids and intravenous immunoglobulin was applied to treat patients with optic neuropathy. Conclusions: This study provides strong evidence that anti-GQ1b antibody syndrome can exhibit visual impairment, which helps further expand the clinical spectrum of anti-GQ1b antibody syndrome. More attention should be paid to the physical and supplementary ophthalmological examination to explore the pathogenesis and treatment of anti-GQ1b antibody syndrome.

PKD1, the locus most commonly affected by mutations that produce autosomal dominant polycystic kidney disease (ADPKD), has previously been localized to chromosome 16p13.3. Since no cytogenetic abnormalities have been found in association with ADPKD, flanking genetic markers have been required to define an interval--the PKD1 region--that contains the PKD1 gene. In this report we demonstrate, through the construction of a long-range restriction map that links the flanking genetic markers GGG1 (D16S84) and 26.6PROX (D16S125), that the PKD1 gene lies within an extremely CpG-rich 750-kb segment of chromosome 16p13.3. Approximately 90% of this region has been cloned in three extensive cosmid/bacteriophage contigs. The cloned DNA is a valuable resource for identifying new closer flanking genetic markers and for isolating candidate genes from the region.

Twins with Duchenne muscular dystrophy (DMD) have been widely studied. We report the first rare case of monozygotic triplets with DMD who shared consistent phenotypes, including delayed motor and language milestones, muscle wasting and weakness, joint contracture, and lumbar lordosis. Muscle magnetic resonance imaging and biopsy revealed the similar muscle injury characteristics and dystrophin absence. Short tandem repeat analysis confirmed monozygosity. A de novo mutation (exon 49-52 deletion) was found in the triplets but not in their mother. Treatment included prednisone, idebenone, and rehabilitation management. At the 2-year follow-up, motor function had deteriorated, and muscle fatty infiltration was more extensive and severe. Our case offers a unique opportunity for genetic and therapeutic research. Furthermore, it highlights the critical role of genetic factors in DMD phenotypes and provides a potential choice for treatment observations. (C) 2021 Published by Elsevier B.V.

目的 对杜兴型肌营养不良症动物模型mdx鼠的关键基因和通路进行分析,探索mdx鼠的发病机制,为DMD的潜在治疗靶点研究奠定基础.方法 从GEO(Gene Expression Omnibus)数据库中筛选纳入GSE7187、GSE64418和GSE52766数据集,分别筛选出3个数据集中的mdx鼠的差异表达基因(differentially ex-pressed genes,DEGs),对3个数据集中重合的DEGs进行基因本体论分析、富集信号通路分析和蛋白质网络互作分析并筛选出10个网络重要节点作为关键基因.结果 3个数据集共同的DEGs有68个,其中61个基因表达上调,7个基因表达下调.GO分析发现DEGs主要与免疫系统过程有关,KEGG分析发现DEGs参与了与炎症反应和免疫反应相关的通路.Tyrobq、Emr1、C1qb、Ly86、C1qc、C1qa、Lyz2、Ms4a6d、Fcer1g和Fcgr3是mdx鼠的关键基因.结论 mdx鼠发病与免疫反应和炎症反应有关,本研究筛选出的关键基因提示了DMD新的治疗靶点.

Objective To report one case of autosomal recessive juvenile⁃onset Parkinson's diseased (AR⁃JP), and summarize its clinical manifestations, imaging and genetic testing results, treatment and outcome. Methods and Results A female patient, 27 years old, clinically manifested as stiffness, inflexibility and involuntary shaking of limbs. Her second sister had similar symptoms. 18F⁃DOPA PET showed decreased dopamine metabolism in the posterior striatum of both sides. Genetic testing showed that the patient had a heterozygous deletion of the PRKN gene exon 12 c.1321T＞C (p.Cys441Arg) and LRRK2⁃41 (MUT) G2019S and SNCA⁃2 (MUT) A30P mutations, which were caused by disease variants. The final diagnosis was AR⁃JP, and she was treated with dopasrazide. The symptoms were significantly reduced but dyskinesia occurred. The dose of dopasrazide was reduced and the combination of trihexyphenidyl and procassone was used. The symptoms were relieved. No dyskinesias and "switching phenomenon" were seen. Conclusions AR⁃JP is caused by a compound heterozygous mutation in the PRKN gene. The treatment of levodopa is effective, and the combination of diphenhexol and procassol has a better effect, and can reduce dyskinesia and "switching". Early diagnosis and timely treatment of AR⁃JP are of great significance to the prognosis of patients.

Background: Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessively inherited neuromuscular disorders caused by deletions, duplications, or small mutations in the DMD gene. With advances in prenatal diagnosis decreasing the number of affected offspring from carrier mothers, the frequency of de novo variants could increase. Therefore, determining the differences between the carrier and de novo variants of the DMD gene, which are rarely explored, is important for trial planning and genetic diagnosis in the future. Methods: A total of 440 patients, 349 of whom had DMD and 91 had BMD, diagnosed in our department between 2012 and 2019, along with their respective mothers, were included in this study. Multiplex ligation-dependent probe amplification was used to detected deletions and duplications in patients and their mothers. Small mutations were detected using next-generation sequencing in the patients, followed by Sanger sequencing in the mothers. Results: Deletions, duplications, and small mutations were identified in 204, 46, and 99 of the 349 patients with DMD and in 50, 10, and 31 of the 91 patients with BMD, respectively. De novo deletions were more concentrated in hotspot regions than carrier deletions of DMD/BMD. No clear bias was observed in the variant distribution between carriers, de novo duplications, and small mutations in DMD/BMD. The carrier frequency of DMD (61.6%) was lower than that of BMD (69.2%), but the difference was not statistically significant. The carrier frequency of deletions of the DMD gene (51.2%) was significantly lower than those of duplications (75%) and small mutations (81.5%). Conclusion: Compared to de novo deletions, deletions from carrier mothers had a wider distribution. Moreover, there was no significant difference between the carrier frequencies of DMD and BMD. Duplications and small mutations were more commonly inherited, while deletions were present de novo .

In recent years, great progress has been made in the treatment of neurogenetic diseases. Specific drugs have been used to treat diseases that were uncurable in the past, and there are noteworthy curative effects. For example, oral intake of PCT124 can improve the squatting and walking ability of children with Duchenne muscular dystrophy. Intrathecal injection of Nusinersen Sodium enables children with spinal muscular atrophy 2 to stand and walk. Meanwhile, specific treatment in the early stages of the disease should be emphasized. In addition, this paper put forward my views on the issues that need attention during the specific drug therapy, as well as the comprehensive treatment such as nutrition, nursing and rehabilitation after the therapy.

The current c l i n i c a l t re a t m e n t f o r a d u l t s e v e re pneumonia often involves the maintenance of vital signs, a large number of antibiotics and hormones and other methods.However, due to the increase of the highrisk host of infection, multiple infections, bacterial resistance, multidrug resistance, and other phenomena are becoming more and more serious.The therapeutic effect is not obvious, while the Xuebijing injection, which contains safflower, red peony root, Chuanxiong (Ligustricum striatum), red sage (Salvia miltiorrhiza) and angelica, is based on the theory of promoting blood circulation and removing blood stasis.All

Review question / Objective: Whether Qilong capsule can effectively treat ischemic stroke compared to conventional intervention regimes or western medicine alone?Condition being studied: Stroke is a common cerebrovascular disease in the world, which is characterized by high incidence, high disability rate, high mortality rate and high recurrence rate.According to the statistical analysis of the global disease burden from 1990 to 2016, stroke was the second leading cause of death in the world in 2016, with 80 million cases of stroke worldwide, of which ischemic stroke accounted for the majority (84.4%).Qilong capsule has the effect of replenishing qi and activating blood circulation, removing blood stasis and dredging collaterals, and is used for the treatment of ischemic stroke (TCM syndrome differentiation is qi deficiency and blood stasis syndrome).Studies have confirmed that Qilong capsule can improve the neurological impairment of qi deficiency and blood stasis syndrome in acute ischemic stroke, reduce the content of Pselectin and inhibit platelet activation.At present, there is no systematic study on the efficacy and safety of Qilong capsule in the treatment of ischemic stroke, so it is necessary to conduct a systematic evaluation and meta analysis to provide evidence-based evidence for Qilong capsule in the treatment of ischemic stroke.

Background: Duchenne muscular dystrophy (DMD) is a fatal, X-linked recessive muscle disorder characterized by heterogeneous progression and severity. We aimed to study the effects of single nucleotide polymorphisms (SNPs) in SPP1 and LTBP4 on DMD progression in Chinese patients.Methods: We genotyped LTBP4 haplotypes and the SPP1 promoter SNPs rs28357094, rs11730582, and rs17524488 in 326 patients registered in the neuromuscular database of The First Affiliated Hospital of Sun Yat-sen University. Kaplan-Meier curves and log-rank tests were used to estimate and compare median age at loss of ambulation, while Cox proportional hazard regression models were used as to analyze the effects of glucocorticoids treatments, DMD genotype, and SPP1/LTBP4 SNPs on loss of ambulation.Results: The CC/CT genotype at rs11730582 was associated with a 1.33-year delay in ambulation loss (p = 0.006), with hazard ratio 0.63 (p = 0.008), in patients with truncated DMD genotype and undergoing steroid treatment. On the other hand, rs17524488 in SPP1 and the IAAM/IAAM haplotype in LTBP4 were not associated with time to ambulation loss.Conclusions:SPP1 rs11730582 is a genetic modifier of the long-term effects of steroid treatment in Chinese DMD patients. Thus, any future clinical study in DMD should adjust for glucocorticoids use, DMD genotype, and SPP1 polymorphisms.

Objective To explore the diversity of clinical manifestations and gene mutations of riboflavin⁃responsive multiple acyl⁃coenzyme A dehydrogenase deficiency (MADD). Methods and Results The clinical, blood biochemical, EMG, muscle biopsy and genetic analysis results of 5 patients with riboflavin⁃responsive MADD were collected, to analyze and summarize the clinical characteristics of riboflavin⁃responsive MADD. The onset age of 5 patients was 13-32 years old, with an average age of 20.40 years old. The main manifestation was fluctuating or progressive muscle weakness, involving facial, neck, proximal limb and respiratory muscles and often aggravated after exercise, fatigue, and infection. Serum creatine kinase (CK) increased slightly to moderately in 5 patients, and blood lactic acid increased significantlyafterexercisein2patients. The EMG of 4 patients showed myogenic damage, and the EMG of one patient showed neurogenic damage in the early stage of the disease and mainly myopathic damage in laterstage. Muscle biopsy of 2 patients showed a large amount of lipid droplet deposition in muscle fibers positive for oil red O staining. Genetic analysis revealed that 4 patients showed homozygous or compound heterozygous mutations in the ETFDH gene(one patient carried homozygous mutations of G250A; 2patients carried compound heterozygous mutations of G250A and G524A; one patient carried compound heterozygous mutations of T1211C and C1454G), the remaining one case carried the G1399C heterozygous mutationin ETFDH geneandthe C725T heterozygousmutationin ETFB gene. Conclusions In mainland of China, riboflavin⁃responsive MADD mainly presents as a lipid deposition disease involving skeletal muscle, with a progressive or fluctuating course. It is easily misdiagnosed as several types of muscular dystrophy, mitochondrial myopathy, glycogen storage disease, myasthenia gravis and peripheral neuropathy. Themutation ETFDH gene is its main cause. Since riboflavin⁃responsive MADD has a good prognosis, the vitamin B2 diagnostic treatment should be given when the patients are suspected of riboflavin⁃responsive MADD, combined with urine organic acid, blood acylcarnitine, muscle biopsy and genetic analysis to confirm the diagnosis. DOI：10.3969/j.issn.1672⁃6731.2020.06.011

Objective To summarize the phenotype and genotype of a family of Becker muscular dystrophy (BMD) caused by a novel missense mutation of DMD gene. Methods and Results Clinical data of one BMD proband and the family members were collected. Next-generation sequencing technology was used to detect possible gene mutation in the proband, a 25-year-old male BMD patient. Sanger sequencing technology was used to further detect possible mutation of c.4449T > G (p.Asn1483Lys) locus of DMD gene in the proband's mother and younger sister. The analysis was carried out combined with clinical data of the proband and other family members. Results showed the patient had the same phenotype as his two uncles (mother's brothers), who presented pseudohypertrophy of calf muscles, atrophy and weakness of proximal lower extremities and elevated serum creatine kinase (CK). Gene mutation analysis demonstrated a novel missense mutation c.4449T > G (p.Asn1483Lys) in exon 34 of DMD gene in the proband. The proband's mother and younger sister were carriers of mutated gene. Combined with the clinical manifestations of proband's uncles, the patient was clearly diagnosed as BMD, and the family was clearly diagnosed as BMD pedigree. Besides, there was a common separation phenomenon in the family. Conclusions The study described a novel missense mutation in exon 34 c.4449T > G (p.Asn1483Lys) of DMD gene which caused BMD. This enriches the mutation map of DMD gene, and also provides valuable information for genetic counseling and prenatal diagnosis. DOI: 10.3969/j.issn.1672-6731.2019.05.008

DOI: 10.3969/j.issn.1672-6731.2019.05.001

Objective To summarize the clinical features and electrophysiological characteristics of stiff-person syndrome (SPS). Methods and Results Clinical data of 11 SPS patients [8 were classic and 3 were stiff-person plus syndrome (SPPS)], who were diagnosed and treated from August 2009 to November 2018, were retrospectively collected. They mainly presented paroxysmal muscle stiffness and pain spasm under stimulation or emotional excitement. The first affected sites were at trunk (4 cases) or limb (7 cases) muscles, and by the time of diagnosis, were mainly at truck muscles (8 cases). Anti-glutamic acid decarboxylase (GAD) antibody testing was positive in 6 cases. Electromyography (EMG) of all the patients showed continuous motor unit activity (CMUA) in the affected muscles at rest state. After treated by benzodiazepines, motor unit potential (MUP) obviously decreased or even disappeared in 6 patients. Conclusions Stiff-person syndrome is a rare autoimmune disease with multiple initial sites, atypical initial symptoms and difficulty in early diagnosis. It should be distinguished from many diseases such as familiar hyperekplexia, tetanus, myotonia congenita and multiple sclerosis (MS). DOI: 10.3969/j.issn.1672-6731.2019.06.005

背景 婴儿型糖原贮积症Ⅱ型(GSDⅡ)患儿临床表现危重,未予重组人酸性α葡糖苷酶替代治疗时,常会在1岁前死于心力衰竭和或呼吸衰竭,目前国内缺少对婴儿型GSDⅡ酶替代治疗的疗效评估.目的 总结婴儿型GSDⅡ使用重组α葡萄糖苷酶治疗的效果,为临床治疗提供参考.方法 收集2016年3月—2017年12月在中山大学附属第一医院住院确诊的婴儿型GSDⅡ患儿3例,均有心肌肥厚和/或肌无力表现,外周血酸性α-葡糖苷酶(GAA)活性低于正常.患儿均接受重组人类GAA替代治疗,20 mg/kg,1次/2周.观测患儿生命体征、呼吸情况、肌力、丙氨酸氨基转氨酶(ALT)、天冬氨酸氨基转氨酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶(CK)、胸部X线检查情况.结果 3例患儿开始治疗时症状均以四肢肌无力并呼吸困难为主要表现,1例成功撤离呼吸机,2例放弃治疗后死亡.3例患儿经重组人类GAA替代治疗肌力均明显好转,ALT下降2例,升高1例;AST下降2例,升高1例;LDH下降1例,升高2例;CK下降2例,升高1例;3例患儿治疗前的胸部X线检查示心影大;治疗后患儿1、2胸部X线检查示心影缩小,患儿3胸部X线检查示心影变化不明显.治疗后心脏彩超示室间隔厚度下降3例;左心室射血分数提升3例.结论 结合文献复习,重组人GAA替代治疗婴儿型GSDⅡ安全有效,可明显改善患儿心功能、肌力及呼吸功能.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscular weakness and atrophy caused by degeneration of brain stem and spinal cord motor neurons. SMA is common genetic neuromuscular disorder that causes infant death. The pathogenesis is survival motor neuron (SMN) protein deletion caused by homozygous disruption of SMN1 gene. Greater knowledge of the molecular basis of SMA pathogenesis has fuelled the development of potential therapeutic approaches, reduced mortality and improved the life quality of SMA patients. The therapeutic strategies include a modified antisense oligonucleotide (ASO), adeno-associated virus (AAV) mediated SMN1 gene replacement therapy, oral small molecular drugs which upregulated SMN protein expression, muscle activating drugs, and neuroprotective drugs, etc. DOI: 10.3969/j.issn.1672-6731.2019.06.003

Facioscapulohumeral muscular dystrophy (FSHD) is a common hereditary neuromuscular disease which is divided into FSHD1 and FSHD2. After years of research, FSHD has established complete molecular diagnostic methods, in which Southern blotting is commonly applied in the diagnosis of FSHD1, and molecular combing (MC) is a novel and simple one. The pathogenesis of FSHD is not yet fully understood, and recent studies have found that it is associated with complex genetic and epigenetic causes. At present, the most recognized molecular mechanism for FSHD is the abnormal expression of DUX4 gene. In addition, the abnormal epigenetic changes in the D4Z4 tandem repeat sequence of 4q region were involved in the pathogenesis of FSHD. There is no cure for FSHD, and some progress has been made in some precise treatment methods for its pathogenesis, such as toxic DUX4 protein removal. In this paper, the diagnosis, pathogenesis and treatment history of FSHD are summarized, so that readers understand the history and present situation of FSHD research. DOI: 10.3969/j.issn.1672-6731.2019.05.003

Objective To investigate the clinical phenotype and genotype of facioscapulohumeral muscular dystrophy type 1 (FSHD1) and the correlation between the two. Methods The clinical data, genotype and laboratory examination of 25 patients with FSHD1 diagnosed by fluorescence in situ hybridization (FISH) from January 2017 to September 2018 were collected. Clinical Severity Score (CSS) was performed according to muscle involvement, and was corrected by age. Age-corrected CSS in 2 groups of patients with different 4qA D4Z4 repeat number was compared with two-independent-sample t test. The relation of D4Z4 repeat number with age-corrected CSS and age of onset were analyzed by using Spearman rank correlation analysis. Results The age-corrected CSS of patients with D4Z4 repeat number of 2-3 was significantly higher than that of patients with D4Z4 repeat number of 4-6. The age-corrected CSS of patients was negatively correlated with the number of D4Z4 repeat in 4qA (r = -0.619, P = 0.001) and the age of onset was positively correlated with the number of D4Z4 in 4qA (r = 0.516, P = 0.012). Conclusions The number of D4Z4 repeat in 4qA of FSHD1 patients is negatively correlated with the clinical severity. Genotype can help to indicate the clinical severity of FSHD1. At the same time, there are factors that affect the clinical severity of FSHD1 in addition to genotype. DOI: 10.3969/j.issn.1672-6731.2019.05.007

In recent years, the clinical trials of Duchenne muscular dystrophy (DMD) gene therapy in foreign countries have proved to be of certain curative effect and good safety. In China, DMD, with a large number of patients, has been introduced into the first rare diseases catalog, indicating that gene therapy will soon enter our country. It is a revolutionary treatment for DMD, and thus clinicians, patients and their families, relevant government departments, charity foundations and media shall prepare for the era of DMD gene therapy, which will benefit for DMD patients. DOI: 10.3969/j.issn.1672-6731.2019.05.002