Obesity and pericallosal lipoma in X-linked emery-dreifuss muscular dystrophy:A case report-Does Emerin play a role in adipocyte differentiation?

Emery dreifuss muscular dystrophy(EDMD) is a rare genetic syndrome consisting of tendon retractions,progressive muscle atrophy and cardiac involvement.We report a case of an obese patient affected by the familial X-linked form in which a pericallosal lipoma was found during investigation for a suspected acute vasculopathy.To date,EDMD has never been associated with cerebral lipomas and the X-linked form was never considered to be involved in lipodystrophic syndromes or non-muscular conditions.Our case confirms the variable expressivity of the disease and suggests a possible role of Emerin in the intranuclear regulation of signals for adipocyte cell differentiation.

The resistive range of motion exercise training in Duchenne muscular dystrophy:a case study

Background:To determine the effectiveness of resistive range of motion exercises in improving muscle strength and functional abilities in Duchenne muscular dystrophy.The study was also aimed to determine if resistive range of motion exercises can slow down the progression of the disease.Methods:A seven-year-old male child was diagnosed with Duchenne muscle dystrophy presented to outpatient physiotherapy clinic.The patient was presented with difficulty in stair climbing,sitting up from the floor,fatigue,and muscle weakness specifically weakness in the proximal limb muscles.The progressive resistive range of motion training was implemented for four years to improve muscle strength and functional abilities.The medical research council grading scale,north ambulatory assessment scale,and creatine kinase were used to evaluate muscle strength,functional abilities,and creatine kinase levels.Results:The muscular strength and functional abilities did not improve after four years of exercise training.The creatine kinase levels were decreased over the period of four years.Conclusion:Resistive range of motion exercises are helpful in maintaining the muscular strength and functional abilities in Duchenne muscular dystrophy.

Surgical and long-term functional outcomes of patients with Duchenne muscular dystrophy following spinal deformity correction

BACKGROUND Life expectancy in patients with Duchenne muscular dystrophy(DMD)has improved due to advances in medical care.DMD patients develop progressive spinal deformity after loss of ambulatory function and onset of wheelchair dependence for mobility.There is limited published data on the effect of spinal deformity correction on long-term functional outcomes,quality of life(QoL),and satisfaction in DMD patients.AIM To investigate the long-term functional outcomes following spinal deformity correction in DMD patients.METHODS This was a retrospective cohort study from 2000-2022.Data was collected from hospital records and radiographs.At follow-up,patients completed the muscular dystrophy spine questionnaire(MDSQ).Statistical analysis was performed by linear regression analysis and ANOVA to analyse clinical and radiographic factors significantly associated with MDSQ scores.RESULTS Forty-three patients were included with mean age 14.4 years at surgery.Spinopelvic fusion was performed in 41.9%of patients.Mean surgical time was 352.1 min and mean blood loss was 36%of estimated total blood volume.Mean hospital stay was 14.1 d.Postoperative complications occurred in 25.6%of patients.Mean preoperative scoliosis was 58°,pelvic obliquity 16.4°,thoracic kyphosis 55.8°,lumbar lordosis 11.1°,coronal balance 3.8 cm,and sagittal balance+6.1 cm.Mean surgical correction of scoliosis was 79.2%and of pelvic obliquity was 80.8%.Mean follow-up was 10.9 years(range:2-22.5).Twenty-four patients had died at follow-up.Sixteen patients completed the MDSQ at mean age 25.4 years(range 15.2-37.3).Two patients were bed-ridden and 7 were on ventilatory support.Mean MDSQ total score was 38.1.All 16 patients were satisfied with the results of spinal surgery and would choose surgery again if offered.Most patients(87.5%)reported no severe back pain at follow-up.Factors significantly associated with functional outcomes(MDSQ total score)included greater duration of post-operative follow-up,age,scoliosis postoperatively,correction of scoliosis,increased lumbar lordosis postoperatively,and greater age at loss of independent ambulation.CONCLUSION Spinal deformity correction in DMD patients leads to positive long-term effects on QoL and high patient satisfaction.These results support spinal deformity correction to improve long-term QoL in DMD patients.

Tetramethylpyrazine Nitrone Improved Motor Deficits and Alleviated Dystrophic Muscle Pathology in the <i>mdx</i>Mouse Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive neuromuscular disorder caused by mutations in the dystrophin encoding gene, with the characteristics of a severe and progressive destruction of muscle structure and function. Skeletal muscle fibrosis is one of the pathological features of DMD. Tetramethylpyrazine (2,3,5,6-tetramethylpyrazine, TMP) has been demonstrated to reduce heart and liver fibrosis. Meanwhile, previous studies showed that Tetramethylpyrazine nitrone (TBN), a nitrone derivative of TMP, has promising therapeutic effects in several neurodegenerative models and is more potent than TMP. In this study, we investigated the potential effect of TBN on the mdx mouse model of DMD. Eight-week-old mdx mice were administered with TBN (30 mg/kg) intragastrically twice daily, with deflazacort (1 mg/kg) once a day as a positive control, for a total of 24 weeks. Behavioral tests including pole-climbing open-field test were monitored every 4 weeks. Histopathological assessment was conducted in the gastrocnemius and diaphragm muscles. The effects of TBN on protein levels of dysferlin were measured by immunohistochemistry. TBN significantly reduced the climbing time in pole test and increased the total distance moved in an open-field test of mdx mice. TBN attenuated fibrosis in the gastrocnemius and diaphragmatic muscles. In addition, TBN protected gastrocnemius muscle fibers via increasing expression of the dysferlin in mdx mice. In conclusion, this study demonstrated that TBN could improve the motor deficits and muscle pathology of mdx mouse, and it is worth further exploring the mechanism of action of TBN for DMD treatment.

Stem cell transplantation for treating Duchenne muscular dystrophy A Web of Science-based literature analysis

OBJECTIVE： To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; （b） original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and （c） publication between 2002 and 2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） documents that were not published in the public domain; and （c） corrected papers. MAIN OUTCOME MEASURES： （1）Annual publication output; （2） distribution according to subject areas; （3） distribution according to journals; （4） distribution according to country; （5） distribution according to institution; （6） distribution according to institution in China; （7） distribution according to institution that cooperated with Chinese institutions; （8） top-cited articles from 2002 to 2006; （9） top-cited articles from 2007 to 2011. RESULTS： A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation for treating Duchenne muscular dystrophy. CONCLUSION： The publications on stem cell transplantation for treating Duchenne muscular dystrophy were relatively few. It also needs more research to confirm that stem cell therapy is a reliable treatment for Duchenne muscular dystrophy.

Adipose-derived stem cells enhance myogenic differentiation in the mdx mouse model of muscular dystrophy via paracrine signaling

Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiation in muscular dystrophy. Adipose-derived stem cells （6 × 106） were injected into the gastrocnemius muscle of mdx mice at various sites. Dystrophin expression was found in the muscle fibers. Phosphorylation levels of Akt, mammalian target of rapamycin （mTOR）, eIF-4E binding protein 1 and $6 kinase 1 were increased, and the Akt/mTOR pathway was activated. Simultaneously, myogenin levels were increased, whereas cleaved caspase 3 and vimentin levels were decreased. Necrosis and fibrosis were reduced in the muscle fibers. These findings suggest that adipose-derived stem cells promote the re- generation and survival of muscle cells by inhibiting apoptosis and fibrosis, thereby alleviating muscle damage in muscular dystrophy.

Umbilical cord mesenchymal stem cell transplantation for the treatment of Duchenne muscular dystrophy

Due to their relative abundance,stable biological properties and excellent reproductive activity,umbilical cord mesenchymal stem cells have previously been utilized for the treatment of Duchenne muscular dystrophy,which is a muscular atrophy disease.Three patients who were clinically and pathologically diagnosed with Duchenne muscular dystrophy were transplanted with umbilical cord mesenchymal stem cells by intravenous infusion,in combination with multi-point intramuscular injection.They were followed up for 12 months after cell transplantation.Results showed that clinical symptoms significantly improved,daily living activity and muscle strength were enhanced,the sero-enzyme,electromyogram,and MRI scans showed improvement,and dystrophin was expressed in the muscle cell membrane.Hematoxylin-eosin staining of a muscle biopsy revealed that muscle fibers were well arranged,fibrous degeneration was alleviated,and fat infiltration was improved.These pieces of evidence suggest that umbilical cord mesenchymal stem cell transplantation can be considered as a new regimen for Duchenne muscular dystrophy.

Limb-girdle muscular dystrophy subtypes First-reported cohort from northeastern China

The relative frequencies of different subtypes of limb-girdle muscular dystrophies vary widely among different populations. We estimated the percentage of limb-girdle muscular dystrophy subtypes in Chinese people based on 68 patients with limb-girdle muscular dystrophy from the Myology Clinic, Neurology Department, First Hospital of Jilin University, China. A diagnosis of calpainopathy was made in 12 cases （17%）, and dysferlin deficiency in 10 cases （15%）. Two biopsies revealed α-sarcoglycan deficiency （3%）, and two others revealed a lack of caveolin-3 （3%）. A diagnosis of unclassified limb-girdle muscular dystrophy was made in the remaining patients （62%）. The ap-pearances of calpain 3- and dysferlin-deficient biopsies were similar, though rimmed vacuoles were unique to dysferlinopathy, while inflammatory infiltrates were present in both these limb-girdle muscular dystrophy type 2D biopsies. Macrophages were detected in seven dysferlinopathy biop-sies. The results of this study suggest that the distribution of limb-girdle muscular dystrophy sub-types in the Han Chinese population is similar to that reported in the West. The less necrotic, re-generating and inflammatory appearance of limb-girdle muscular dystrophy type 2A, but with more lobulated fibers, supports the idea that calpainopathy is a less active, but more chronic disease than dysferlinopathy. Unusual features indicated an extended limb-girdle muscular dystrophy disease spectrum. The use of acid phosphatase stain should be considered in suspected dysferlinopathies. To the best of our knowledge, this is the first report to define the relative proportions of the various forms of limb-girdle muscular dystrophy in China, based on protein testing.

A NEW APPROACH TO GENE DIAGNOSIS OF DUCHENNE/BECKER MUSCULAR DYSTROPHY──AMPLIFIED FRAGMENT LENGTH POLYMORPHISM

Four (CA)n repeats, located in introns 44, 45, 49 and 50 of the dystrophin gene., were evaluated in Chinese. These loci are highly polymorphic, with polymorphism information contents of 0. 872, 0. 772, 0. 870 and 0. 718, respectively. All four loci can be easily amplified and labelled using two duplex PCR reactions with α-32P-dCTP and can be detected by denaturing polyacrylamide gel electrophoresis. Using these four loci and the two polymorphic (CA)n repeats located at the 5' and 3' ends of the dystrophin gene, we have developed a new PCR-based procedure -Amp-FLP (amplified fragment length polymorphism) linkage analysis for the gene diagnosis of DMD/BMD. This method can detect intragenic recombination rapidly and efficiently and greatly. improves the success rate of carrier detection and prenatal diagnosis in non-deletion DMD/BMD families. All of the loci used in this procedure are intragenic. In addition, the loci in introns 44. 45, 49 and 50 are located in the deletion-prone region of the dystrophin gene, making them valuable and useful in the identification of deletion mutations. Here we report one case of deletion detection using these four loci.

Expression of tissue inhibitor of metalloproteinase-1 in progression muscular dystrophy

Objective Tissue inhibitor of metalloproteinase-1 （TIMP-1） is a muhifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy （PMD）. Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy （DMD）, Becker muscular dystrophy （BMD） , congenital muscular dystrophy （CMD） by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP- 1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD.

Anesthesia management in a pediatric patient with Becker muscular dystrophy undergoing laparoscopic surgery:A case report

BACKGROUND Patients with Becker muscular dystrophy(BMD)have a high risk of developing hyperkalemia,rhabdomyolysis,and malignant hyperthermia when exposed to volatile anesthetics and depolarizing muscle relaxants.Patients with BMD are also prone to respiratory depression after general anesthesia.Thus,it is extremely challenging for anesthesiologists to manage anesthesia in BMD patients,particularly in pediatric BMD patients.Here,we present successful anesthesia management using transversus abdominis plane block(TAPB)combined with total intravenous anesthesia(TIVA)in a pediatric BMD patient undergoing laparoscopic inguinal hernia repair.CASE SUMMARY A 2-year-old boy,weighing 15 kg,with BMD,was scheduled for laparoscopic inguinal hernia repair.TIVA was used for induction,and continuous infusions of short-acting intravenous anesthetics combined with TAPB were performed for anesthesia maintenance.Moreover,TAPB provided good postoperative analgesia.The patient underwent uneventful surgery and anesthesia,and over the 17 mo follow-up period showed no anesthesia-induced complications.CONCLUSION TAPB combined with TIVA,using short-acting intravenous anesthetic agents,can provide safe and effective anesthesia management in pediatric BMD patients undergoing short-term abdominal surgery.

Congenital muscular dystrophy caused by beta1,3-Nacetylgalactosaminyltransferase 2 gene mutation:Two case reports

BACKGROUND Mutations in the beta1,3-N-acetylgalactosaminyltransferase 2(B3GALNT2)gene can lead to impaired glycosylation ofα-dystroglycan,which,in turn,causes congenital muscular dystrophy(CMD).The clinical phenotypes of CMD are broad,and there are only a few reports of CMD worldwide.CASE SUMMARY This report describes the cases of two children with CMD caused by B3GALNT2 gene mutation.The main manifestations of the two cases were abnormal walking posture,language development delay,and abnormal development of the white matter.Case 2 also had unreported symptoms of meningocele and giant arachnoid cyst.Both cases had compound heterozygous mutations of the B3GALNT2 gene,each containing a truncated mutation and a missense mutation,and three of the four loci had not been reported.Nineteen patients with CMD caused by B3GALNT2 gene mutation were found in the literature.Summary and analysis of the characteristics of CMD caused by B3GALNT2 gene mutation showed that 100%of the cases had nervous system involvement.Head magnetic resonance imaging often showed abnormal manifestations,and more than half of the children had eye and muscle involvement;some of the gene-related symptoms were self-healing.CONCLUSION B3GALNT2 gene can be used as one of the candidate genes for screening CMD,cognitive development retardation,epilepsy,and multiple brain developmental malformations in infants.

Myocardial Protection with Beta Blocker Treatment in Infants with Heart Failure Due to Congenital Heart Defects and Duchenne Muscular Dystrophy

Our first intention to treat infants’ heart failure with beta blockers was to improve the clinical condition as shown in our prospective randomized trial. We only use non-selective beta blockers in these infants, carvedilol in those with left ventricular dysfunction and propranolol in those with congenital heart disease without ventricular dysfunction. Despite a significant improvement of Ross’s heart failure score, we could not convince most colleagues within the last 25 years if the concept of neurohumoral activation in heart failure is not well-established pediatric cardiology. Recently, Honghai Liu et al. published that cardiomyocyte cytokinesis failure was increased in congenital heart disease. Inactivation of the beta adreno receptors genes and administration of the beta-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the number of cardiomyocytes (endowment) and conferred benefit after myocardial infarction in adults. We currently realize that propranolol in infants with congenital heart disease not only decrease highly elevated NT-Pro-BNP values but also decrease cardiac troponin T values that may indicate myocardial injury due to neurohumoral activation. We reproduce this observation, primarily seen in infants with congenital heart disease, in an infant with Duchenne muscular dystrophy. These observations were in good accordance with current data from H. Liu et al., who showed that treatment with non-selective beta blockers early after birth might rescue cytokinesis defects and prevent heart dysfunction in adulthood in a mouse model.

Ventilation function changes in patients with Duchenne muscular dystrophy under and over 12 years of age Analysis of 65 cases

BACKGROUND：Previous studies indicate that vital capacity in patients with Duchenne muscular dystrophy increases with age when they are under 12 years old, and decreases from 13 or 14 years of age; however, recent studies indicate that the vital capacity in patients with Duchenne muscular dystrophy begins to decrease even before 12 years of age. OBJECTIVE： To verify if the vital capacity in patients with Duchenne muscular dystrophy decreases before the age of 12 years and to observe the effect of rehabilitation exercise on vital capacity. DESIGN, TIME AND SETTING： The case analysis was performed at the Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University （Guangzhou, Guangdong Province, China） from December 2004 to January 2006. PARTICIPANTS： Sixty-five male patients diagnosed as having Duchenne muscular dystrophy and who underwent pulmonary ventilation function examination at the Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University （Guangzhou, Guangdong Province, China） from December 2004 to January 2006; ages ranged from 6 to 22 years old. METHODS： The ventilation function of 65 patients was determined using a Sensor Medics 2100 pulmonary function test apparatus （USA）, and the data obtained were subjected to statistical analysis comparing patients under 12 years of age and those above 13 years of age, and comparing those who performed rehabilitation exercise with those who did not. MAIN OUTCOME MEASURES： Forced vital capacity （FVC）; forced expiratory volume in one second （FEV1）; maximal voluntary ventilation （MMV）; the ratio of forced expiratory volume in one second and forced vital capacity （FEV1/FVC）; each measured value as a percentage of the corresponding predicted value. RESULTS： There were no significant differences in FVC, FEV1 and MMV between patients under 12 years of age and those above 13 years of age （P 〉 0.05）. The FVC, FEV1 and MMV values, as percentages of the predicted values, were, in patients under 12 years old, significantly higher than those in patients older than 13 （P 〈 0.05）. All ventilation function parameters except FEV1/FVC in patients undergoing rehabilitation exercise were higher than those in patients without rehabilitation exercise. This difference was not significant in patients under 12 years of age, but was statistically significant in those older than 13 years （P 〈 0.05）. CONCLUSION： Although the values of ventilation function measured increase with age in Duchenne muscular dystrophy patients less than 12 years of age, real ventilation function is already damaged. Thirteen years of age is an important time point for pulmonary function change. Rehabilitation exercise can slow down the process of pulmonary function exacerbation in Duchenne muscular dystrophy patients, especially when therapy starts before 12 years of age.

优化多重PCR检测Duchenne muscular dystrophy基因外显

目的:介绍一种快速简便地优化多重PCR检测DMD基因外显子缺失的方法及详细步骤.方法:采2ml外周血,用0.2%氯化钠处理收集白细胞,再用基因组DNA提取试剂盒抽提基因组DNA,用优化的多重PCR法直接检测DMD基因外显子的缺失.结果:用该方法检测DMD基因外显子缺失结果准确清晰.结论:用优化的多重PCR技术可以直接检测DMD基因外显子缺失,跟通常使用的9对引物一步法相比,具有经济、快速、简便等特点.

Homozygous deletion, c. 1114-1116del, in exon 8 of the CRPPA gene causes congenital muscular dystrophy in Chinese family: A case report

BACKGROUND Congenital muscular dystrophy(CMD)is a clinically and genetically heterogeneous group of inherited muscle disorders.Mutations in the CRPPA gene(encoding CDPLribitol pyrophosphorylase A)are recognized as causative factors of dystroglycanopathies,a subtype of CMD with defects in glycosylation.CASE SUMMARY The present study examined a Chinese family,whose proband presented mainly with muscle weakness in both lower limbs but without brain and eye symptoms.In this family,a homozygous deletion,c.1114-1116del(p.V372del),was identified in exon 8 of CRPPA in the proband,while a heterozygous deletion was identified in the proband’s father and mother,who lacked symptoms.A mild dystroglycanopathy of CMD was diagnosed.CONCLUSION The findings of this study expanded the clinical and mutational spectrum of patients with CMD associated with CRPPA mutations.

THE MECHANISM OF CEREBRAL EVOKED POTENTIALS BY REPETITIVE MAGNETIC STIMULATION OF GASTROCNEMIUS MUSCLE IN DUCHENNE MUSCULAR DYSTROPHY

Objective. To study the features and mechanism of the cerebral evoked potentials by repetitive stimulation of calf muscle in Duchenne muscular dystrophy (DMD) patients with obvious muscular dystrophy and psuedohypertrophy. Methods. Cerebral evoked potentials by stimulation of calf muscles and somatosensory evoked potentials (SEPs) by the stimulation of posterior tibial nerves at ankle were measured in 10 patients with DMD and 10 normal controls matched with gender and age. The intensity of the magnetic stimulation was at 30％ of maximal output (2.1 Tesla, MagPro magnetic stimulator, Dantec) and the frequency was 1 Hz. The low intensity of magnetic stimulation was just sufficient to produce a contraction of the muscle belly underneath the coil. Recording electrode was placed at 2 cm posterior to the Cz, reference to Fpz. The latencies of N33, P38, N48 and P55 and amplitude (P38－ N48) were recorded. SEPs were recorded by routine methods. Results. In normal subjects, the amplitudes of cerebral evoked potentials by magnetic stimulation of calf muscle was 40％ lower than that by electrical stimulation of the posterior tibial nerves at ankle. The latency of P38 was 2.9± 2.1 ms longer compared with electrical stimulation of the posterior tibial nerves at ankle. In 6 patients, P38 latency from magnetic stimulation was remarkably prolonged (P< 0.01), and in 4 patients, there was no remarkable response. SEPs evoked by electrical stimulation were normal in all of the patients. Conclusion. DMD is an available model for the study of mechanism of cerebral evoked potentials by magnetic stimulating muscle. We can conclude that the responses from magnetic stimulation were produced by muscle input. The abnormal responses in patients may relate to decreased input of muscle by stimulating dystrophic and psedohypertrophic muscle.

Clinical manifestations and prenatal diagnosis of Ullrich congenital muscular dystrophy: A case report

BACKGROUND Ullrich congenital muscular dystrophy(UCMD)is one of the collagen-VI-related myopathies caused by mutations of COL6A1,COL6A2,and COL6A3 genes.Affected individuals are characterized by muscle weakness,proximal joint contracture,distal joint hyperlaxity,and progressive respiratory failure.There is currently no cure for UCMD.Here,we report the clinical manifestations and prenatal diagnosis of compound heterozygous mutations of the COL6A2 gene in a Chinese family with UCMD.CASE SUMMARY A 3-year-old boy,his 4-year-old brother,their parents,and a 20-wk-old fetus in the mother’s womb were included in the study.The brothers had the typical manifestations of the early-severe subtype:A delayed motor milestone(never walking independently),torticollis,scoliosis,proximal joint contracture,distal joint hyperextension,right hip joint dislocation,and calcaneal protuberance.Both brothers were found by whole-exome sequencing and Sanger sequencing to carry two mutations of the COL6A2 gene(c.1353_c.1354insC,p.Arg453Profs-Ter42/c.2105G>A,p.Trp702Ter).The absence of collagen VI staining in the younger brother’s muscle was identified accurately.Genetic counseling and prenatal diagnosis were crucial for the family,as the autosomal recessive genetic disease affected a quarter of the patient’s siblings.The fetus of the mother’s third child underwent prenatal diagnosis and carried the same two mutations of COL6A2,confirmed in the amniotic fluid by multiplex ligation-dependent probe amplification and short tandem repeats.After a painful psychological struggle,the parents finally decided to terminate the pregnancy.CONCLUSION We report a Chinese family suffering from UCMD.By clarifying the COL6A2 mutations in the probands,the parents had the opportunity to opt for voluntary interruption of the third UCMD pregnancy.

Cardiac involvement in Duchenne and Becker muscular dystrophy

Duchenne and Becker muscular dystrophy(DMD/BMD) are X-linked muscular diseases responsible for over 80% of all muscular dystrophies. Cardiac disease is a common manifestation,not necessarily related to the degree of skeletal myopathy; it may be the predominant manifestation with or without any other evidence of muscular disease. Death is usually due to ventricular dysfunction,heart block or malignant arrhythmias. Not only DMD/BMD patients,but also female carriers may present cardiac involvement. Clinically overt heart failure in dystrophinopathies may be delayed or absent,due to relative physical inactivity. The commonest electrocardiographic findings include conduction defects,arrhythmias(supraventricular or ventricular),hypertrophy and evidence of myocardial necrosis. Echocardiography can assess a marked variability of left ventricular dysfunction,independently of age of onset or mutation groups. Cardiovascular magnetic resonance(CMR) has documented a pattern of epicardial fibrosis in both dystrophinopathies' patients and carriers that can be observed even if overt muscular disease is absent. Recently,new CMR techniques,such as postcontrast myocardial T1 mapping,have been used in Duchenne muscular dystrophy to detect diffuse myocardial fibrosis. A combined approach using clinical assessment and CMR evaluation may motivate early cardioprotective treatment in both patients and asymptomatic carriers and delay the development of serious cardiac complications.

T2 Mapping and Fat Quantification of Thigh Muscles in Children with Duchenne Muscular Dystrophy

Quantitative magnetic resonance image(MRI)in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy(DMD).The purpose of this study w批to measure丁2 relaxation time of thigh muscles in children with DMD and healthy boys,and to correlate the T2 relaxation time of muscles with the fat fraction(FF)at quantitative magnetic resonance and results of clinical assessment.Thirty-two boys with DMD and 18 healthy boys were evaluated with T2 mapping and three-point Dixon MRI.Age,body mass index(BMI),muscle strength assessment,timed functional tests(time to walk or run 10 metres,rise from the floor and ascend four stairs),and the North Star Ambulatory Assessment(NSAA)were evaluated.Spearman’s correlation was used to assess the relationships between FF and clinical assessments and T2 relaxation time.The mean T2 relaxation time of thigh muscles in DMD was significantly longer than that in the control group(P<0.05),except for the gracilis(P=0.952).The gracilis,sartorius and adductor longus were relatively spared by fatty infiltration in DMD patients.The T2 relaxation time was correlated significantly with the mean FF in all muscles.Age,BMI,total muscle strength score,timed functional tests and NSAA were significantly correlated with the overall mean T2 relaxation time.T2 mapping may prove clinically useful in monitoring muscle changes as a result of the disease process and in predicting the outcome of DMD patients.