Milder course in Duchenne patients with nonsense mutations and no muscle dystrophin

Duchenne muscular dystrophy (DMD), a severe and lethal condition, is caused by the absence of muscle dystrophin. Therapeutic trials aiming at the amelioration of muscle function have been targeting the production of muscle dystrophin in affected Duchenne patients. However, how much dystrophin is required to rescue the DMD phenotype remains an open question. We have previously identified two exceptional golden retriever muscular dystrophy (GRMD) dogs with a milder course despite the total absence of muscle dystrophin. Here we report two unusual patients carrying nonsense mutations in the DMD gene and dystrophin deficiency but with an unexpectedly mild phenotype. Three reported polymorphisms, respectively in genes LTBP4, SPP1 and ACTN3 were excluded as possible DMD genetic modifiers in our patients. Finding the mechanisms that protect some rare patients and dogs from the deleterious effect of absent muscle dystrophin is of utmost importance and may lead to new avenues for treatment. Importantly, these observations indicate that it is possible to have a functional large muscle even without dystrophin.     

假肥大型肌营养不良症的基因突变和产前诊断研究

目的 了解中国人群DMD基因外显子突变的特点和产前诊断情况.方法 应用多重连接依赖性探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)和变性高效液相色谱(denaturing high performance liquid chromatography,DHPLC)技术对Duchenne型假肥大型肌营养不良症(Duchenne muscular dystrophy,DMD)患者及胎儿进行DMD基因检测并对结果进行统计分析.结果 在388例DMD患者中发现缺失、重复和点突变3种突变类型,其中缺失突变230例,占59.28％,重复突变43例,占11.08％.共发现2个缺失热点区域,分别涉及第45～54外显子和第3～19外显子.重复突变主要位于第2～43外显子之间.发现点突变115例,占29.64％.对其中6例进行检测共发现5例点突变.在53例产前诊断中,共发现33例男胎,其中18例为患病胎儿.患病家庭在已知同意的前提下自主选择了终止妊娠.结论 中国人DMD基因的突变特点与国外报道一致.产前诊断可避免DMD患儿出生.     

Reflex sympathetic dystrophy arising in a patient with familial Mediterranean fever

A 14-year-old girl with familial Mediterranean fever (FMF) had had acute attacks of fever, abdominal pain, and arthritis for 4 years. Her last arthritis attack was protracted, leading to reflex sympathetic dystrophy (RSD) in her right lower extremity. Physical therapy along with sympathetic ganglion block and corticosteroid therapy was used for the treatment. To our knowledge, this is the first reported case of RSD arising in a patient with FMF. Early recognition of RSD in FMF patients is important, and physical therapy should be applied along with medical treatment. Received: 26 March 1999 / Accepted: 20 July 1999     

Novel splice site mutation in CNNM4 gene in a family with Jalili syndrome

Jalili syndrome is a rare autosomal recessive genetic disease characterized by the association of amelogenesis imperfecta and cone-rod retinal dystrophy. This syndrome is caused by mutations in the CNNM4 gene. Different types of CNNM4 mutations have been reported; missense, nonsense, large deletions, single base insertion, and duplication.We used Sanger sequencing to analyze a large consanguineous family with three siblings affected with Jalili syndrome, suspected clinically after dental and ophthalmological examination. These patients are carrying a novel homozygous mutation in the splice site acceptor of intron 3 (c.1682-1G > C) in the CNNM4 gene.We compare the findings of the present family to those from literature, in order to further delineate Jalili syndrome.     

16. Complex Regional Pain Syndrome

Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy is a pain syndrome with an unclear pathophysiology and unpredictable clinical course. The disease is often therapy resistant, the natural course not always favorable. The diagnosis of CRPS is based on signs and symptoms derived from medical history and physical examination. Pharmacological pain management and physical rehabilitation of limb function are the main pillars of therapy and should be started as early as possible. If, however, there is no improvement of limb function and persistent severe pain, interventional pain management techniques may be considered. Intravenous regional blocks with guanethidine did not prove superior to placebo but frequent side effects occurred.Therefore this technique receives a negative recommendation (2 A–). Sympathetic block is the interventional treatment of first choice and has a 2 B+ rating. Ganglion stellatum (stellate ganglion) block with repeated local anesthetic injections or by radiofrequency denervation after positive diagnostic block is documented in prospective and retrospective trials in patients suffering from upper limb CRPS. Lumbar sympathetic blocks can be performed with repeated local anesthetic injections. For a more prolonged lumbar sympathetic block radiofrequency treatment is preferred over phenol neurolysis because effects are comparable whereas the risk for side effects is lower (2 B+). For patients suffering from CRPS refractory to conventional treatment and sympathetic blocks, plexus brachialis block or continuous epidural infusion analgesia coupled with exercise therapy may be tried (2 C+). Spinal cord stimulation is recommended if other treatments fail to improve pain and dysfunction (2 B+). Alternatively peripheral nerve stimulation can be considered, preferentially in study conditions (2 C+).     

骨髓间充质干细胞移植治疗杜氏型进行性肌营养不良症344例临床疗效分析

目的 探讨自体骨髓间充质干细胞(MSCs)及脐带间充质干细胞移植治疗杜氏型进行性肌营养不良症的临床疗效.方法 2007年6月～2008年6月该科室应用自体MSCs移植对344例杜氏型肌营养不良症患者进行治疗,采用治疗前后对照方法进行研究.骨髓间充质干细胞制备:对344例患者皮下注射粒细胞集落刺激因子,剂量为每日每公斤体重5～10μg,动员骨髓干细胞,共4 d,4 d后采集骨髓,将采集的骨髓通过Percoll梯度离心,提取单个核细胞(MNC),总量为(5.72±1.89)X108,CD34+细胞(2.67±1.22)%,CD133+细胞(1.79±0.73)%.培养骨髓单个核细胞7～10d,最终得到骨髓间充质干细胞含量为(1.90±0.96)X10s.应用四肢肌肉内注射的方式进行干细胞移植.移植后3、6、9、12个月观察患者酶学、肌电图、肌肉MRI变化,评价干细胞移植前后日常生活活动能力(ADL)、临床分级.结果 344例患者中292名患者四肢肌肉力量均有所改善.总有效率为85.00%,好转患者中199名患者四肢力量明显好转,明显好转率为58.00%;93名患者四肢肌力较前略好转,好转率为37.00%.结论 自体骨髓干细胞移植可使杜氏型肌营养不良症患者肌力得到改善,生活质量得到提高.     

强直性肌营养不良症一家系4例临床分析

目的探讨强直性肌营养不良症(DM)的临床特点。方法对我院2008年收治的1例确诊的DM患者及其家系中另3例确诊DM患者的临床资料进行分析。结果 4例患者,男性2例,女性2例,均隐袭起病,以肌强直、肌无力、肌萎缩为主要表现,伴有内分泌和生殖系统、心脏、眼睛等多系统损害,肌强直放电和肌源性损害是DM的主要肌电图特征。结论 DM是一组以肌无力、肌强直和肌萎缩为特点的多系统受累的常染色体显性遗传病,临床表现复杂多样,阳性家族史和肌电图对诊断有重要意义。