Analysis of intercellular communication patterns in facioscapulohumeral muscular dystrophy based on single-cell nuclear transcriptome sequencing / 国际生物医学工程杂志

Objective:To analyze the patterns of intercellular communication in facioscapulohumeral muscular dystrophy (FSHD) by single-cell nuclear transcriptome sequencing.Methods:Bilateral asymmetrical lesions mouth orbicular muscle of two patients with FSHD and mouth orbicular muscle of two healthy patients were selected. Six samples were obtained, and were divided into control group, mild group and severe group. The normal orbicularis muscle sample was collected from 2 healthy individuals (the control group). The muscle samples in the mild group were from two patients with relatively normal muscle sides, and the samples in the severe group were from two patients with more severe muscle damage sides. Single-cell nuclear transcriptome sequencing was performed on all cells of the three groups. Reduced dimension clustering and cell definition were performed to identify differentially expressed genes and enrichment pathways. Intercellular communication patterns among major cell types and key signaling pathways were explored by cellular communication analysis.Results:Differential gene expression analysis of FSHD bilateral muscle samples identified 46 functionally differentially expressed genes associated with the disease in different cell types, related to apoptosis, oxidative stress, immune inflammation, and muscle function. Intercellular communication was generally increased in the severe group. Fibro-adipogenic progenitors (FAPs) and macrophages are important signaling sources in the abnormal muscle microenvironment of FSHD and are closely associated with disease progression. There are six unique signaling pathways in the mild group, including bone morphogenetic proteins (BMP), transforming growth factor-β (TGF-β), CXC motif chemokine ligand (CXCL), adhesion G protein-coupled receptor E5 (ADGRE5), interleukin-16 (IL-16), and wingless-type MMTV integration site family (WNT) signaling pathways. These signaling pathways are mainly involved in the interaction between macrophages, FAPs, and adipocytes and may be involved in the regulation of fat deposition and fibrosis changes in the diseased muscle.Conclusions:Single-cell nuclear transcriptome sequencing provides a relatively comprehensive pattern of intercellular communication between key cell types in FSHD, providing an appropriate reference for understanding the intercellular regulatory mechanisms of the FSHD muscle microenvironment.

Abordaje rehabilitador de paciente con distrofia facioescapulohumeral y fractura de cadera / Rehabilitative Approach to a Patient with Facioscapulohumeral Dystrophy and Hip Fracture

La distrofia facioescapulohumeral es una miopatía progresiva de base genética, con gran variabilidad fenotípica. Se caracteriza por la progresión de cambios distróficos en la dirección cráneo-caudal con lesiones asimétricas de los músculos faciales, cintura escapular, hombros y piernas. Se expone este caso con el objetivo de demostrar la importancia de la rehabilitación en el manejo integral de pacientes con distrofia muscular y fractura de cadera. Se presenta el abordaje rehabilitador en una paciente con distrofia facioescapulohumeral y fractura de cadera tratada mediante artroplastia total de cadera. El tratamiento rehabilitador precoz contribuyó a mejorar el control del dolor y su recuperación funcional(AU)

Facioscapulohumeral dystrophy is a genetically based progressive myopathy (4q35), with great phenotypic variability. It is characterized by the progression of dystrophic changes in the craniocaudal direction with asymmetric lesions of the facial muscles, shoulder girdle, shoulders, and legs. We report the rehabilitation approach in a female patient with facioscapulohumeral dystrophy and hip fracture treated by total hip arthroplasty. A rehabilitation program was included and improvement in pain control and functionality was observed. Rehabilitation is a fundamental pillar in the comprehensive management of patients with muscular dystrophy and hip fracture(AU)

Speech and swallowing characteristics in patients with facioscapulohumeral muscular dystrophy / Caracterização da fala e da deglutição em pacientes com distrofia muscular facioescapuloumeral

ABSTRACT Background: Although facial muscle weakness is common in patients with Facioscapulohumeral Muscular Dystrophy (FSHD), the literature is scarce on the speech and swallowing aspects. Objective: To investigate speech and swallowing patterns in FSHD and assess the correlation with clinical data. Methods: A cross-sectional study was conducted. Patients with clinical confirmation of FSHD and aged above 18 years were included and paired with healthy control individuals by age and gender. Individuals who had neurological conditions that could interfere with test results were excluded. The following assessments were applied: speech tests (acoustic and auditory-perceptual analysis); swallowing tests with the Northwestern Dysphagia Patient Check Sheet (NDPCS), the Eat Assessment Tool (EAT-10), the Speech Therapy Protocol for Dysphagia Risk (PARD), and the Functional Oral Intake Scale (FOIS); disease staging using the modified Gardner-Medwin-Walton scale (GMWS); and quality of life with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The correlation between test results and clinical data was verified by non-parametric statistics. Results: Thirteen individuals with FSHD and 10 healthy controls were evaluated. The groups presented significant differences in the motor bases of phonation and breathing. Regarding swallowing, two (15%) individuals presented mild dysphagia and seven (53.8%) showed reduced facial muscles strength. These results were not correlated with duration of the disease, age at symptoms onset, and quality of life. Dysphagia was related to worsening disease severity. Conclusions: FSHD patients presented mild dysarthria and dysphagia. Frequent monitoring of these symptoms could be an important way to provide early rehabilitation and better quality of life.

RESUMO Antecedentes: Embora haja predomínio de fraqueza muscular facial na distrofia facioescapuloumeral (FSHD), é escassa a literatura sobre aspectos de fala e deglutição. Objetivo: Investigar os padrões de fala e deglutição na FSHD e correlacioná-los com dados clínicos da doença. Métodos: Estudo transversal. Pacientes com confirmação clínica de FSHD e idade acima de 18 anos foram incluídos e pareados por idade e sexo com controles saudáveis. Foram excluídos indivíduos que apresentassem condições neurológicas que pudessem interferir nos resultados dos testes. Aplicaram-se as seguintes avaliações: fala (análise acústica e perceptivo-auditiva); deglutição, por meio do Northwestern Dysphagia Patient Check Sheet (NDPCS), Eat Assessment Tool (EAT-10), Protocolo de Avaliação para Risco de Disfagia (PARD) e Functional Oral Intake Scale (FOIS); estadiamento da doença, por meio da Gardner-Medwin-Walton scale (GMWS); e qualidade de vida, com o Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Resultados de fala e deglutição foram correlacionados com dados clínicos da doença por teste não paramétrico. Resultados: Foram avaliados 13 indivíduos com FSHD e dez controles saudáveis. Houve diferença significativa entre os grupos nas bases motoras fonação e respiração. Na deglutição, dois (15%) indivíduos apresentaram disfagia leve e sete (53,8%), força reduzida da musculatura da face. Esses resultados não foram correlacionados com tempo de doença, idade de início dos sintomas e qualidade de vida. A disfagia esteve relacionada com a gravidade da doença. Conclusões: Pacientes com FSHD apresentaram disartria e disfagia leves. O monitoramento frequente desses sintomas pode ser uma forma importante de proporcionar reabilitação precoce e melhor qualidade de vida.

Early-onset facioscapulohumeral muscular dystrophy with Coats syndrome: a case report / 中华神经科杂志

Early-onset facioscapulohumeral muscular dystrophy is a rare clinical syndrome characterized by severe muscle weakness started in early childhood,with extramuscular manifestations such as retinal vascular tortuosity,sensorineural hearing loss and epilepsy.Herein we report a case with early-onset facioscapulohumeral muscular dystrophy and Coats syndrome.Early diagnosis of Coats syndrome is critical for the prognosis.

A "Triple Trouble" Case of Facioscapulohumeral Muscular Dystrophy Accompanied by Peripheral Neuropathy and Myoclonic Epilepsy / 中华医学杂志(英文版)

<p><b>Background</b>Facioscapulohumeral muscular dystrophy (FSHD) is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a "complex disease plus" patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy.</p><p><b>Methods</b>Standard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification (MLPA), whole exome sequencing (WES), and targeted methylation sequencing.</p><p><b>Results</b>The patient presented with mild facial weakness, humeral poly-hill sign, scapular winging, peroneal weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore, electrophysiology revealed severely demyelinated and axonal injury. The muscle and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated nerve fibers that significantly decreased with thin myelinated fibers and onion bulbs changes. Generalized sharp and sharp-slow wave complexes on electroencephalography support the diagnosis toward myoclonic epilepsy. In addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI fragment and permissive allele A, which corresponded with D4Z4 hypomethylation status in the family. Both the patient's mother and brother only presented the typical FSHD but lacked overlapping syndromes. However, no mutations for hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA and WES.</p><p><b>Conclusions</b>The present study described a "tripe trouble" with FSHD, peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping syndromes and contributing to the credible diagnosis of atypical phenotype. It would provide a direct clue on medical care and genetic counseling.</p>

FAT1 Gene Alteration in Facioscapulohumeral Muscular Dystrophy Type 1

Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array. Recent studies revealed that the FAT1 expression is associated with disease activity of FSHD, and the FAT1 alterations result in myopathy with a FSHD-like phenotype. We describe a 59-year-old woman with both contracted D4Z4 repeat units and a FAT1 mutation. Shoulder girdle muscle weakness developed at the age of 56 years, and was followed by proximal leg weakness. When we examined her at 59 years of age, she displayed asymmetric and predominant weakness of facial and proximal muscles. Muscle biopsy showed increased variation in fiber size and multifocal degenerating fibers with lymphocytic infiltration. Southern blot analysis revealed 8 D4Z4 repeat units, and targeted sequencing of modifier genes demonstrated the c.10331 A>G variant in the FAT1 gene. This FAT1 variant has previously been reported as pathogenic variant in a patient with FSHD-like phenotype. Our study is the first report of a FAT1 mutation in a FSHD1 patient, and suggests that FAT1 alterations might work as a genetic modifier.

Bilateral Cochlear Implantation in Facioscapulohumeral Muscular Dystrophy Presenting Sensorineural Hearing Loss / 대한이비인후과학회지

Facioscapulohumeral muscular dystrophy (FSHD) presents a muscular weakness in the face, shoulder girdle, and legs. In addition, bilateral, progressive, high-frequency sensorineural hearing loss (SNHL) can be expressed. A 3-year-old boy visited with bilateral facial paralysis and bilateral hearing loss. Audiological evaluations revealed bilateral, progressive, sloping SNHL and bilateral hearing aids was used for more than 3 years. Cochlear implantation was carried out on left side when he was 6 years old and on right side when he was 7 years old. Seven months after cochlear implantation on left side, his shoulder muscle weakness was found and the genetic analysis showed decreased D4Z4 repeat size in 4qA allele confirming a diagnosis of FSHD. After auditory rehabilitation using electroacoustic stimulation, his hearing and speech perception were much improved. This case suggests that cochlear implantation can be beneficial in patients with SNHL associated with FSHD.

Distrofia muscular facioescapulohumeral en Chile: presentación de serie en hospital de referencia terciario / Facioscapulohumeral muscular dystrophy: Report of seven patients

Background: Facioscapulohumeral muscular dystrophy is the third most common muscular dystrophy with an estimated prevalence of 1 per 20.000 and a normal life expectancy in the majority of patients. However, approximately 15% of patients become wheelchair bound in the course of their life. It is a hereditary autosomal dominant disease with high (95%) penetrance by the age of 20, but with variable degree of phenotypic expression even in the same family group. Symptoms frequently start in the second decade of life, with facial and scapular weakness. Aim: To report the clinical features of seven patients with the disease, seen at a public hospital. Material and Methods: Analysis of seven patients with genetic study seen in a public Hospital in Santiago. Results: The age of patients fluctuated from 18 to 61 years and four were females. The mean age at onset of symptoms was 29 years and four had a family history of the disease. The usual presenting complaint was arm or shoulder asymmetric weakness. Four patients had bone pain. Facial involvement was present in four. A genetic study was done in five patients, the other two patients were relatives, confirming the contraction or lower number of repetitions in D4Z4 region. After 12 years of follow up only 2 patients older than 60 years cannot work and one female patients is in a semi dependent state at the age of 30. Conclusions: The clinical workup in the diagnosis and the timely indication of genetic studies are highlighted, to avoid unnecessary and invasive procedures. The variability in the phenotypic expression in a similar genetic defect is discussed and the genetic or epigenetic mechanisms of this muscular dystrophy are described.

Beevor’s Sign: A Review.

Beevor’s sign named after Charles Edward Beevor is one of the eponymous medical signs in the dictionary of neurologists. The present article reviews the history and the pathophysiology of Beevor’s sign. This sign is famous in Facioscapulohumeral muscular dystrophy and in the spinal cord injuries of T10. There are very few researches done regarding Beevor’s sign and a little can be found in the history. On eliciting the sign, one can observe caudal movement of navel on cervical flexion. In normal individuals the position of umbilicus does not change but in patients of Facioscapulohumeral muscular dystrophy, spinal crod lesion T10 or myopathy, the umbilicus is seen to move towards the head. Very few studies have been done regarding other diseases where Beevor’s sign is seen but a lot of studies have been done on fasiculohumeral dystrophy and Beevor’s sign. Research is needed in other diseases showing positive Beevor’s sign and its management.

Characteristics of facioscapulohumeral muscular dystrophy's vascular inflammatory pathological changes / 中华神经科杂志

Objective To investigate the pathological features of blood vessel inflammation in facioscapulohumeral muscular dystrophy ( FSHD ) and the role of vasculitis on the pathogenesis of FSHD. Methods The clinical manifestations and myopathological features of 26 FSHD patients were retrospectively analyzed and summarized. All of the patients were divided into 2 groups; inflammatory infiltration group and non-inflammatory infiltration group. The latter was further divided into 3 subgroups;endomysial inflammation subgroup, perivasculitis subgroup and transmural vasculitis subgroup.Immunohistochemical staining were carried out in inflammatory infiltration group with anti-CD3, anti-CD4,anti-CD8,anti-CD20 and anti-SMA antibody. The control group was composed of 10 dermatomyositis ( DM)cases and 10 polymyositis ( PM) cases. Results The age of onset was (25. 2 ± 12. 6) years old and the average course was (7. 8 ±7. 3) years. The sex ratio of male to female was 1.6: 1. Five of them had family history. The main clinical features were progressive weakness and atrophy of facial, shoulder girdles and proximal upper limbs muscles. The lower distal limbs and (or) lower distal limbs and pelvic girdle muscles were involved in 18 cases. The main pathological features were shown as followed. Seventeen of them had focal inflammatory cell infiltration, including endomysial inflammation (4/17) , perivasculitis (7/17) , and transmural vasculitis (6/17). Immunohistochemical staining confirmed the major types of inflammatory cells were CD4* T lymphocytes and CD20B lymphocytes, which was familiar with DM. While in PM, CD8+ T lymphocytes were dominant The proportionality of residual muscle fibers obviously decreased in inflammatory infiltration group ( 48. 0% ± 23. 6% ) than non-inflammatory infiltration group ( 94. 3% ±3. 1% , T = 198. 000, P = 0. 000). As to CK levels, there were no significant deviation. Conclusions Obvious inflammatory cell infiltration can be seen in FSHD, the locations of inflammatory cells are endomyosium inflammation, perivasculitis and transmural vasculitis. Transmural vasculitis indicates vascular pathological factor may have something to do with pathogenesis of FSHD.

Genetic diagnosis of facioscapulohumeral muscular dystrophy by real-time fluorescent quantitative polymerase chain reaction / 中华神经科杂志

Objective To develop a convenient, rapid and specific method using real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) for detection of facioscapulohumeral muscular dystrophy(FSHD). Methods Genomic DNA was extracted and digested by restricted endonuclease EcoR Ⅰ , followed by agarose electrophoresis. The DNA (< 38 kb) was retrieved from agarose electrophoretic gels. The primers and probe were designed in D4ZA gene in chromosome 4. One hundred and fifteen subjects were examined by FQ-PCR using the retrieved DNA (<38 kb) as a template and the result was analyzed by fluorescent curve comparing with positive control. Results The results by FQ-PCR showed that 13 cases were positive in 16 FSHD cases whose EcoR Ⅰ fragment sizes were known, 75 cases were negative in 78 cases of normal controls, 15 cases were positive in 16 FSHD cases diagnosed clinically whose EcoR Ⅰ fragment sizes were unknown, and 3 cases were positive in 5 cases of relatives of FSHD patients. Consistency was checked using Kappa index between the 2 gene diagnostic tests for FSHD (FQ-PCR test and the traditional Southern blotting test), and between the 2 diagnostic criterions (gene diagnosis by FQ-PCR and clinical diagnosis). The results were statistically significant (κ = 0. 765, P = 0. 002 ; κ = 0. 844, P = 0. 000). Conclusions A new genetic diagnostic method of FSHD by FQ-PCR was developed, which was more simplified and reliable compared to the time-consuming, radioactive Southern blotting. It could also detect the D4Z4 arrays in cases having deletion of p13E-11 as well as the interchromosomal exchange between 4q35 and 10q26. The new method of FQ-PCR for FSHD may be extended to utilize clinically in future.

Clinical Features and Genetic Analysis of Fascioscapulohumeral Muscular Dystrophy

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is associated with contractions of the polymorphic D4Z4-repeat array in 4q35 and has the distinctive clinical presentation of an initial involvement of the facial, shoulder-girdle, and upper-arm muscles. The aim of the present study was to determine clinical characteristics in Korean patients with FSHD and potential relationships between contracted D4Z4-repeat size and the FSHD phenotype. METHODS: We studied 34 genetically confirmed patients who had repeat sizes less than 38 kb, and analyzed their clinical manifestations with a structured protocol. The expressed phenotypes were scored according to the Clinical Severity Score formulated by Ricci and van Overveld. RESULTS: The clinical spectrum ranged widely, from asymptomatic individuals with minimal signs to wheelchair- bound patients. The initial affects were mainly in the facial muscles (68.8%), followed by the shoulder-girdle muscle (28.1%). Asymmetric features of the face and shoulder girdle were also important findings (71.9% and 90.0%, respectively). Winging scapular (87.5%), transverse smile (84.4%), Beevor's sign (68.8%), and sleeping with eyes opened (59.4%) were clinically important signs. There was a significant negative correlation between repeat size and clinical severity (r=-0.38, p=0.03). CONCLUSIONS: Distinctive clinical characteristics of FSHD are descending progression and asymmetric distribution of the muscle weakness. Our results also confirmed that the severity of FSHD increases with decreasing D4Z4-repeat size.

Avaliação dos resultados da artrodese da articulação escapulotorácica no tratamento da escápula alada na distrofia fascioescapulumeral / Evaluation of scapulothoracic arthrodesis results in the treatment of winged scapula in facioscapulohumeral dystrophy

OBJETIVO: Avaliar a técnica cirúrgica da artrodese escapulotorácica na distrofia fascioescapulumeral (DFEU), analisando os resultados e as complicações pós-operatórias. MÉTODOS: No período de fevereiro de 1992 a fevereiro de 2006 foram realizadas oito artrodeses escapulotorácicas em cinco pacientes no Departamento de Ortopedia e Traumatologia da Faculdade de Ciências Médicas da Santa Casa de São Paulo (DOT-FCM-SCSP). Os critérios para indicação cirúrgica foram: dor, déficit funcional do membro acometido, fadiga muscular e deformidade estética. Na técnica cirúrgica empregada para a artrodese foi realizada a fixação da escápula à parede torácica por meio de amarrilho com fios de poliéster n° 5, uma placa metálica estreita e fina, além de colocação de enxerto esponjoso autólogo. RESULTADOS: O seguimento médio dos pacientes foi de 124 meses. Na comparação da amplitude de movimentos pré e pós-operatórios, notou-se melhora na elevação, mantida a rotação lateral, com o UCLA no período pré-operatório variando de 7 a 11 e pós-operatório de 29 a 33. Dentre as complicações, encontraram-se dois casos de pneumotórax, um caso de soltura do material de síntese e um caso de ausência de consolidação óssea. COMENTÁRIO: Obtida consolidação da artrodese em seis casos, além da melhora da dor e elevação. Dois casos foram reoperados, sendo um devido à quebra do material e o outro, à não consolidação. Todos evoluíram para consolidação.

OBJECTIVE: To evaluate the surgical scapulothoracic arthrodesis technique in facioscapulohumeral dystrophy (FSHD) by analyzing post-op results and complications. METHODS: from February 1992 to February 2006, eight scapulothoracic arthrodesis procedures were performed in five patients at the Orthopedics and Traumatology Department of the Medical Sciences School at the Santa Casa Hospital of São Paulo (DOT-FCM-SCSP). The criteria for surgical indication were pain, functional deficit of the limb involved, muscular fatigue, and esthetic deformity. The surgical technique used for the arthrodesis fixated the scapula to the thoracic wall by tying a narrow, slim plate with No. 5 polyester threads and placing an autologous cancellous bone graft. RESULTS: Mean follow-up of the patients was of 124 months. Comparing the range of movement before and after surgery, the authors observed an improvement in raising, lateral rotation being kept, with the pre-op UCLA ranging from 7 to 11, and the post-op UCLA ranging from 29 to 33. Complications included two cases of pneumothorax; one case of the detachment of synthesis material, and one case of lack of bone fusion. COMMENT: Arthrodesis fusion was achieved in six cases, besides improvement in pain and raising. Two cases were reoperated on, one of them due to breakage of the material and another one due to lack of fusion. All cases evolved on to fusion.

Early-Onset Facioscapulohumeral Muscular Dystrophy: Significance of Pelvic Extensor in Sagittal Spinal Imbalance / 대한정형외과학회잡지

An 11-year-old girl with early-onset facioscapulohumeral muscular dystrophy (FSHD) presented with progressive gait disturbance and lumbar hyperlordosis. The motor power of her pelvic extensor muscles was grade 3. Pelvic tilt and hip flexion were markedly increased as determined by gait analysis. This FSHD case is an impressive example of a patient demonstrating the concept that weak pelvic extensor muscles cannot keep the spine upright and balanced. The most important factor in the development of hyperlordosis is the weakness of the pelvic extensor muscles, and the results of gait analysis exquisitely explain the pathophysiology. The patient stands with her spine hyperextended to maintain upright posture by a compensatory mechanism of relatively strong back extensor muscles. Corrective surgery for lumbar hyperlordosis was not considered as it could eliminate the compensatory lumbar hyperextension, thus making the spine of the patient stoop forward through the hip joint during walking, being caused by the weakness of her pelvic extensor muscles.

Facioscapulohumeral Muscular Dystrophy Confirmedby D4Z4 Analysis

No abstract available.

Clinical and Genetic Analysis of Korean Patients with Facioscapulohumeral Muscular Dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominantly inherited muscular disorder, which is characterized by weakness of facial, shoulder and hip girdle, humeral, and anterior distal leg muscles. The FSHD gene has been mapped to 4q35 and a deletion of integral copies of a 3.3-kb DNA repeat motif named D4Z4 was known to be the genetic background of the disorder. Although FSHD is the second most common muscular dystrophy in adulthood, there were few reports on the genetically confirmed patients in Korea. Recently, we experienced four Korean patients with clinical features resembling FSHD. In order to confirm the diagnosis, conventional Southern blot (SB) analysis by using double digestion with EcoRI and BlnI and hybridization with p13E-11 probe was performed in three patients and newly developed long polymerase chain reaction (PCR) method was used for one patient because genomic DNA was not enough for conventional SB for this patient. All patients were demonstrated to have shortened D4Z4 repeats that were consistent with FSHD. Therefore, we could confirm the diagnosis of FSHD in four Korean patients and appropriate genetic counseling was done for the patients and their families. It is of note that long-PCR method could be a good alternative for conventional SB when D4Z4 repeats were less than 5.

Diagnosis of facioscapulohumeral muscular dystrophy using double enzyme digestion associated Southern blotting method / 中华神经科杂志

Objective To develop an operational gene diagnosis method for Chinese Facioscapulohumeral muscular dystrophy (FSHD) patients Methods Genomic DNAwas double digested with restriction enzymes EcoRⅠ/HindⅢ and EcoRI/BlnI,respectively The digested fragments were separated on a 0 6% agarose gel After transferred to a Nytran SuperCharge Membrane, the fragmented DNAs were hybridized with the probe p13E 11 The hybridizing fragments were analyzed by the software ImageMaster Total Lab v1 11 and the size of each band was then given Results Only a 4q35 EcoRI+HindIII/P13E 11 fragment larger than 33 kb was detected in each of the controls Two fragments were detected in each of the 33 FSHD patients, one of which was smaller than 33 kb Although there was also presence of two small alleles in the 3 other FSHD cases, either of them turned out to be 10q26 derived owing to its BlnI sensitivity Interestingly, we found a sporadic patient who carried three 4q35 type fragments and, strikingly, two of them were smaller than 33 kb In the analysis of FSHD family members, a 9 year old boy with no clinical signs was found to share the small fragment with his affected father, indicating that he may be a pre symptomatic patient Conclusion The double digestion associated Southern blotting method we developed can be applied to both the diagnosis of FSHD patients and the prediction of pre symptomatic patients Furthermore, by the gene detection using this method, we first got the evidence of translocation between 4q and 10q in Chinese FSHD patients, which may be helpful to the elucidation of the pathogenesis of FSHD

Prenatal Diagnosis by Direct DNA Analysis in Facioscapulohumeral Muscular Dystrophy (FSHD) Families

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder which has been clinically shown to cause progressive weakness and result in atrophy of the facial muscles, shoulder girdle and upper arm muscles. The responsible gene for the FSHD has been located on chromosome 4q35-qter. The probes p13E-11 and pFR-1 detect DNA rearrangements associated with FSHD as under 28 kb DNA fragment in genomic southern analysis digested with EcoR I and the fragment contains 3.3 kb Kpn I tandem repeats. In this study, 4 fetuses with a family history of FSHD were analysed by genomic southern hybridization analysis with probes to determine whether they carried the deleted region. Of the 4 fetuses, three of them had mothers who were FSHD patients and the other one had a father affected with FSHD. After 10-11 weeks of gestation, we performed chorionic villi sampling and extracted DNA from uncultured and cultured tissue cells for the direct DNA analysis. The result of the southern analysis showed two fetuses having received about 15-18 kb of deleted genes from the father and the mother respectively, and found to be FSHD patients. The other two fetuses were shown to have two normal alleles from the parents and found to be normal. Two pregnancies which were determined to be normal were carried to term delivering two healthy babies.

Shoulder Motion after Scapulothoracic Arthrodesis of the Facioscapulohumeral Type of Progressive Muscular Dystrophy ( PMD ) / 대한정형외과학회잡지

Many patients who have facioscapulohumeral muscular dystrophy eventually have instability of the scapula due to weakness of the muscles which stabilize the scapula. However, a subset of these patients have sufficient strength in the supraspinatus and deltoid muscle to abduct the arm if the scapula has been stabilized. In four patients who had facioscapulohumeral type of progressive muscular dystrophy, scapulothoracic arthrodesis was done for the treatment of limited unstable shoulder motion, especially flexion and abduction and symptomatic winging of the scapula caused by the loss of scapular stability from July 1994 to Feb.1995. The purpose of this study was to report 5 cases who obtained permanent stability after the scapulothoracic arthrodesis and compare the pre- and postoperative glenohumeral motion. The average preoperative active abduction was 74 degrees, which was improved to l35 degrees at the last follow up in 4 cases except unsatisfied 1 case. The average preoperative active flexion was 66 degrees, which improved to 140 degrees at last follow up. The average preoperative UCLA shoulder score was 18.4 points, which improved to 29.6 points at the last follow up. They were doing well in activity of daily living except unsatisfied one case. The scapulothoracic arthrodesis in the facioscapulohumeral type of the progressive muscular dystrophy is successful in achieving scapular stability so it is valuable for selected patients, as it improves appearance, enhances function, and increases tolerance to exercise.