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1.
Rev Neurol (Paris) ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38749790

ABSTRACT

INTRODUCTION: Dropped head syndrome (DHS) is characterized by a chin-on-chest deformity, correctable by passive neck extension. METHODS: Case report. RESULTS: A patient with a heavy nephrological history (dialyzed since 5 years) complained for twenty months about a falling head. The symptomatology was punctuated by dialysis sessions, with aggravation secondary to dialysis. Clinical and paraclinical exploration for neurological, neuromuscular or orthopedic disease was negative. Analysis of the post-dialysis blood pressure showed a slow and gradual decline. From the date the patient became symptomatic, blood pressure was below 80/40mmHg. The correction of blood pressure by increasing midodrine posology resulted in a cure of DHS. DISCUSSION: Considering the negativity of explorations, the cure of symptoms following the correction of arterial hypotension, the rhythmic nature of symptomatology by dialysis, and the recurrence of symptoms concomitantly with drops in blood pressure, we suggested that hypotension was the only etiology explaining this DHS.

2.
Rev Neurol (Paris) ; 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38643028

ABSTRACT

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

3.
Rev Neurol (Paris) ; 179(9): 983-992, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37633734

ABSTRACT

INTRODUCTION: Patients with severe neuromuscular disease (sNMD) are considered at high risk of severe COVID-19. Muscle tissue is often replaced by fibroadipose tissue in these diseases whereas the new mRNA-based vaccines are injected intramuscularly. We aimed at evaluating the efficacy of two injections associated with a booster injection of mRNA vaccine in these patients. METHODS: We performed an observational, prospective, single-centre study to investigate the level of anti-S antibodies (Abs) and their neutralization activity at weeks 6 (W6) and 24 (W24) after two injections of mRNA-1273 vaccine and at weeks 12 (BW12) and 29 (BW29) after a booster injection of BNT162b2 vaccine in patients with sNMD. RESULTS: Thirty-three patients with sNMD were included. At W6, 30 patients (90.1%) showed a protective serum level of specific anti-S Abs with a strong neutralization capacity. We observed a decline over time: only 12 patients (36.3%) retained anti-S Abs levels considered as protective at W24. The neutralization activity remained above the cut off in 23 (69.7%). The booster vaccination restored robust neutralization activity for all analysed 22 patients (100%) at BW12, which was maintained without any significant drop at BW29 (16). No severe adverse event was reported in this cohort and none of the 33 patients developed symptomatic COVID-19 over one year. CONCLUSIONS: This study provides evidence that most sNMD patients receiving two injections of COVID-19 mRNA-based vaccines develop a strong humoral response after vaccination. A decline over time was observed but a single booster injection restores a long-term immunity. Moreover, no safety issues were observed.


Subject(s)
COVID-19 , Neuromuscular Diseases , Humans , SARS-CoV-2 , COVID-19/prevention & control , 2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , Prospective Studies , Vaccination , Antibodies , RNA, Messenger
4.
Rev Neurol (Paris) ; 179(8): 914-922, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37019741

ABSTRACT

Treatment strategies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) must be adapted on a case-to-case basis. Validated and reproducible tools for monitoring treatment response are required at diagnosis, when initiating treatment and throughout follow-up. A task force of French neurologists, experts in neuromuscular disease reference centers, was assembled to provide expert advice on the management of typical CIDP with intravenous immunoglobulins (Ig), and to harmonize treatment practices in public and private hospitals. The task force also referred to the practical experience of treating CIDP with Ig at the diagnostic, induction and follow-up stages, including the assessment and management of Ig dependence, and following the recommendations of the French health agency.


Subject(s)
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Humans , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnosis , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy , Expert Testimony , Immunoglobulins, Intravenous/therapeutic use , France/epidemiology
5.
Rev Neurol (Paris) ; 176(6): 507-515, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32354651

ABSTRACT

In France, the epidemic phase of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in February 2020 and resulted in the implementation of emergency measures and a degradation in the organization of neuromuscular reference centers. In this special context, the French Rare Health Care for Neuromuscular Diseases Network (FILNEMUS) has established guidance in an attempt to homogenize the management of neuromuscular (NM) patients within the French territory. Hospitalization should be reserved for emergencies, the conduct of treatments that cannot be postponed, check-ups for which the diagnostic delay may result in a loss of survival chance, and cardiorespiratory assessments for which the delay could be detrimental to the patient. A national strategy was adopted during a period of 1 to 2months concerning treatments usually administered in hospitalization. NM patients treated with steroid/immunosuppressants for a dysimmune pathology should continue all of their treatments in the absence of any manifestations suggestive of COVID-19. A frequently asked questions (FAQ) sheet has been compiled and updated on the FILNEMUS website. Various support systems for self-rehabilitation and guided exercises have been also provided on the website. In the context of NM diseases, particular attention must be paid to two experimental COVID-19 treatments, hydroxycholoroquine and azithromycin: risk of exacerbation of myasthenia gravis and QT prolongation in patients with pre-existing cardiac involvement. The unfavorable emergency context related to COVID-19 may specially affect the potential for intensive care admission (ICU) for people with NMD. In order to preserve the fairest medical decision, a multidisciplinary working group has listed the neuromuscular diseases with a good prognosis, usually eligible for resuscitation admission in ICU and, for other NM conditions, the positive criteria suggesting a good prognosis. Adaptation of the use of noninvasive ventilation (NIV) make it possible to limit nebulization and continue using NIV in ventilator-dependent patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Neuromuscular Diseases/therapy , Pandemics , Pneumonia, Viral/epidemiology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antimalarials/therapeutic use , Azithromycin/therapeutic use , COVID-19 , Cardiorespiratory Fitness , Coronavirus Infections/drug therapy , Emergency Treatment , France/epidemiology , Glycogen Storage Disease Type II/therapy , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Immune System Diseases/therapy , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Muscular Atrophy, Spinal/drug therapy , Oligonucleotides/therapeutic use , Physical Therapy Modalities , Pneumonia, Viral/drug therapy , Prognosis , RNA, Small Interfering/therapeutic use , SARS-CoV-2 , Steroids/therapeutic use , Withholding Treatment , alpha-Glucosidases/therapeutic use
6.
Rev Med Interne ; 40(2): 70-81, 2019 Feb.
Article in French | MEDLINE | ID: mdl-30527961

ABSTRACT

INTRODUCTION: Dermatomyositis are rare autoimmune diseases. The discovery of specific antibodies such as the anti-TIF1γ, anti-SAE1/2 and anti-NXP2 antibodies has been associated with specific clinical phenotypes. The recent development of standardized kits based on immunodot method is a progress in dermatomyositis diagnosis. Here, we report the clinical characteristics of patients carrying these antibodies with or without clinical setting of dermatomyositis. METHODS: This single-center french retrospective study was conducted from November 2014 to February 2017 at Bordeaux university hospital. Patients carrying anti-TIF1γ, anti-SAE1/2 and anti-NXP2 antibodies, detected by immunodot, were included. RESULTS: Among the 58 patients included, only 10 were finally diagnosed with dermatomyositis. Some form of cancer was found in all anti-TIF1γ antibodies positive patients associated with dermatomyositis. Among the 48 anti-TIF1γ, anti-SAE1/2 and anti-NXP2 antibodies positive patients without clinical phenotype of dermatomyositis, 30 had autoimmune or inflammatory condition and 39 patients presented a significant biological autoimmunity. None of them developed dermatomyositis during the follow-up. CONCLUSION: The immunodot kit allowed the diagnosis of 10 dermatomyositis. A high number of autoantibody positive patients without dermatomyositis raises the issue of the immunodot's performances in the context of biological autoimmunity.


Subject(s)
Adenosine Triphosphatases/immunology , Autoantibodies/blood , DNA-Binding Proteins/immunology , Dermatomyositis/blood , Transcription Factors/immunology , Ubiquitin-Activating Enzymes/immunology , Adult , Aged , Biomarkers/blood , Dermatomyositis/diagnosis , Dermatomyositis/epidemiology , Dermatomyositis/immunology , Female , France/epidemiology , Hospitals, Teaching , Humans , Immunoassay , Male , Middle Aged , Retrospective Studies , Seroepidemiologic Studies
7.
Eur J Neurol ; 25(5): 790-794, 2018 05.
Article in English | MEDLINE | ID: mdl-29437287

ABSTRACT

BACKGROUND AND PURPOSE: The aim was to determine the genetic background of unknown muscular dystrophy in five French families. METHODS: Twelve patients with limb girdle muscular dystrophy or distal myopathy were clinically evaluated. Gene mutations were identified using targeted exon sequencing and mutated DNAJB6 was tested in vitro. RESULTS: Five patients presented with distal lower limb weakness whilst others had proximal presentation with a variable rate of progression starting at the mean age of 38.5 years. Two novel mutations (c.284A>T, p.Asn95Ile, two families; and c.293_295delATG, p.Asp98del, one family) as well as the previously reported c.279C>G (p.Phe93Leu, two families) mutation in DNAJB6 were identified. All showed a reduced capacity to prevent protein aggregation. CONCLUSIONS: The mutational and phenotypical spectrum of DNAJB6-caused muscle disease is larger than previously reported, including also dysphagia. The originally reported c.279C>G (p.Phe93Leu) mutation is now identified in four different populations and appears to be a mutational hotspot. Our report confirms that some DNAJB6 mutations cause distal-onset myopathy and hence DNAJB6 defects should be considered broadly in dominant muscular dystrophy families.


Subject(s)
Distal Myopathies/genetics , HSP40 Heat-Shock Proteins/genetics , Molecular Chaperones/genetics , Muscular Dystrophies, Limb-Girdle/genetics , Mutation , Nerve Tissue Proteins/genetics , Adult , Aged , Aged, 80 and over , Disease Progression , Female , France , Humans , Male , Middle Aged , Muscle Weakness/genetics , Pedigree , Phenotype
8.
Neurol Genet ; 2(6): e112, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27766311

ABSTRACT

OBJECTIVE: In this study, muscle involvement assessed by MRI and levels of GMPPB and glycosylation of α-dystroglycan expression in muscle were examined in patients with limb-girdle muscular dystrophy (LGMD) type 2T. METHODS: Six new patients with genetically verified mutations in GMPPB were studied. T1-weighted magnetic resonance images were obtained in 4 participants. Muscle strength and potential involvement of extramuscular organs were examined. Glycosylation of α-dystroglycan in muscle was studied, and GMPPB and α-dystroglycan expression was analyzed by Western blotting. Prevalence of LGMD2T was calculated from the total LGMD population in Denmark. GMPPB was sequenced in all unclassified cases. RESULTS: Two patients carried 3 new mutations in GMPPB. The other 4 patients carried previously described pathogenic mutations in GMPPB. MRI showed that the paraspinal muscles were the most affected, followed by involvement of hamstrings. Our results showed a loss of glycosylation of α-dystroglycan as well as secondary loss of merosin expression on Western blotting. The prevalence of LGMD2T in the Danish cohort of patients with LGMD is 1.5%. CONCLUSIONS: The new findings of this study are (1) the consistent finding of a preferential affection of paraspinal and hamstring muscles in LGMD2T, (2) 3 new mutations in GMPPB, (3) variable loss of glycosylation tested with IIH6 and VIA4 antibodies, and (4) a prevalence of LGMD2T of 1.5% in a well-characterized Danish LGMD cohort.

9.
Ann R Coll Surg Engl ; 98(8): 547-551, 2016 11.
Article in English | MEDLINE | ID: mdl-27502337

ABSTRACT

INTRODUCTION In the 75-80% of urothelial bladder cancers (UBC) presenting as non-muscle invasive bladder cancer (NMIBC), transurethral resection of bladder tumour (TURBT) is the key treatment and staging procedure. In the 20-25% of patients with muscle invasive bladder cancer (MIBC), further cross-sectional imaging is required to complete the staging process before considering radical treatment. Given the adverse effects of ionising radiation, clinicians identify patients believed to have MIBC, and so requiring further imaging pre-TURBT, at the tumour histology/stage based on the tumour's visual characteristics. There is minimal evidence describing the accuracy of such predictions in newly-diagnosed patients. METHODS Over a 6-year period, a database of patients undergoing resection of newly-diagnosed bladder lesions in a single UK centre was prospectively established. Predictions based on histology were simultaneously recorded, and the accuracy of these predictions of histology/stage subsequently assessed. RESULTS One hundred and twenty two (73.1%) patients with histologically confirmed NMIBC had predictions recorded versus 45 (26.9%) patients with MIBC. Visual assessment predictions of MIBC had a sensitivity of 88.9% (95% confidence interval [CI] 76.5%-95.2%) and a specificity of 91.0% (95% CI 84.6%-94.9%), giving a positive predictive value of 78.4% (95% CI 65.4%-87.5%) and a negative predictive value of 95.7% (95% CI 90.3%-98.1%). CONCLUSIONS We find that visual assessment is accurate in predicting the presence of MIBC. This supports the practice of stratifying patients at the time of initial cystoscopy for those requiring further radiological staging pre-TURBT.


Subject(s)
Cystoscopy , Neoplasm Staging/methods , Urinary Bladder Neoplasms/pathology , Humans , Neoplasm Invasiveness/pathology , Prospective Studies , Sensitivity and Specificity , Urinary Bladder/pathology , Urinary Bladder Neoplasms/diagnosis
11.
Clin Genet ; 89(3): 371-7, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26404489

ABSTRACT

Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and type 2 (OPD1, OPD2), Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). These conditions are clinically characterized by variable skeletal dysplasia associated in males, with extra-skeletal features including brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2 cases and in all instances of typical OPD1 and MNS. Here, we report a series of 10 fetuses and a neonatally deceased newborn displaying a multiple congenital anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We found a global mutation rate of 44%. This series allows expanding the clinical and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to correctly discriminate OPDSD based on clinical criteria in fetuses due to the major overlap between these conditions. Molecular analyses may help pathologists to refine clinical diagnosis according to the type and the location of FLNA mutations. Discriminating the type of OPDSD is of importance in order to improve the genetic counseling to provide to families.


Subject(s)
Craniofacial Abnormalities/genetics , Fetus , Filamins/genetics , Hand Deformities, Congenital/genetics , Mutation , Osteochondrodysplasias/genetics , Phenotype , Craniofacial Abnormalities/diagnosis , Craniofacial Abnormalities/metabolism , DNA Mutational Analysis , Female , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/metabolism , Humans , Infant, Newborn , Male , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/metabolism , Pedigree
12.
Rev Neurol (Paris) ; 169(8-9): 603-12, 2013.
Article in French | MEDLINE | ID: mdl-24011642

ABSTRACT

Autosomal recessive Charcot-Marie-Tooth disease (AR-CMT) is often characterized by onset in early childhood and severe phenotype compared to the dominant forms. CMT disease associated with periaxin gene (PRX) is rare and characterized by demyelination limited to the major peripheral nerves. Following the discovery of a high frequency of a specific periaxin gene mutation (E1085fsX4 homozygote) in the Reunion Island, we examined all French patients known as carriers of the periaxin gene mutation. There were 24 patients. Eighteen were from the Reunion Island (6 families and 10 sporadic cases). The six remaining patients were in two families, each with two affected individuals, and two sporadic cases. The series included 17 female and seven male patients. Walking was acquired late, on average at 3.4±1.6 years. One patient never learned to walk. The Charcot Marie Tooth Neuropathy Score (CMTNS) averaged 24.5±8.1. Seven patients had been wheelchair-bound since the age of 24±22. Other symptoms were: scoliosis most often observed after the age of 12 years and sometimes complicated by a restrictive respiratory syndrome; foot deformity in 24 patients; strabismus; glaucoma; myopia. When conduction recordings are available, median nerve motor conduction was slow (<10m/s), associated with a major lengthening of distal latencies. Study of the periaxin gene should be considered in patients with severe demyelinating neuropathy associated with early infantile scoliosis. This disease leads to major disability (29% of patients in this series were wheelchair-bound) and to respiratory insufficiency. Genetic counselling is highly recommended for consanguineous families.


Subject(s)
Charcot-Marie-Tooth Disease/genetics , Charcot-Marie-Tooth Disease/physiopathology , Membrane Proteins/genetics , Mutation , Adult , Charcot-Marie-Tooth Disease/diagnosis , Child , Child, Preschool , Cohort Studies , Electrophysiology , Family , Female , France , Humans , Infant , Male , Reunion , Young Adult
13.
Rev Neurol (Paris) ; 168(4): 367-70, 2012 Apr.
Article in French | MEDLINE | ID: mdl-22385972

ABSTRACT

Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy is a genetically and clinically heterogeneous group of disorders of the peripheral nervous system. Mutations in multiple genes are currently known. We report an original case of CMT associated with chronic neutropenia in a patient with a K562del mutation in the dynamin 2 (DNM2) gene in a patient presenting with alterated cognitive function. Associated manifestations may guide molecular study.


Subject(s)
Charcot-Marie-Tooth Disease/genetics , Dynamin II/genetics , Mutation , Neutropenia/genetics , Charcot-Marie-Tooth Disease/complications , Genetic Association Studies , Humans , Lysine/genetics , Male , Middle Aged , Mutation/physiology , Neutropenia/complications , Sequence Deletion
14.
Ergonomics ; 54(7): 672-7, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21770754

ABSTRACT

The effect of an accelerometer driven electronic postural monitor (Spineangel®) placed within the electromagnetic measurement field of the Polhemus Fastrak™ is unknown. This study assessed the reliability and accuracy of Fastrak™ linear and angular measurements, when the Spineangel® was placed close to the sensor(s) and transmitter. Bland Altman plots and intraclass correlation coefficient (2,1) were used to determine protocol reproducibility and measurement consistency. Excellent reliability was found for linear and angular measurements (0.96, 95% CI: 0.90-0.99; and 1.00, 95% CI: 1.00-1.00, respectively) with the inclusion of Spineangel®; similar results were found, without the inclusion of Spineangel®, for linear and angular measurements, (0.96, 95% CI: 0.89-0.99; and 1.00, 95% CI: 1.00-1.00, respectively). The greatest linear discrepancies between the two test conditions were found to be less than 3.5 mm, while the greatest angular discrepancies were below 3.5°. As the effect on accuracy was minimal, these findings support the conjoint use of the Fastrak™ during validation studies of the Spineangel® device. STATEMENT OF RELEVANCE: Although previous studies have used the Fastrak™ as the gold standard measurement system, the influence of an accelerometer driven postural monitor on accuracy has not been reported. The strength of the present study has been to determine the effect of accelerometer placement within the electromagnetic field on the reliability and accuracy of the Fastrak™.


Subject(s)
Electromagnetic Fields , Lumbar Vertebrae/physiology , Movement/physiology , Signal Processing, Computer-Assisted/instrumentation , Biomechanical Phenomena , Humans , Posture , Range of Motion, Articular , Reproducibility of Results
17.
Eur J Neurol ; 18(3): 436-41, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20880070

ABSTRACT

BACKGROUND: Multiple mitochondrial DNA (mtDNA) deletions usually have a mendelian inheritance secondary to mutation in nuclear genes. One of these is the Twinkle gene whose mutation is responsible for autosomal dominant progressive external ophthalmoplegia (PEO). The number of reported cases with mainly myopathic symptoms and possible nervous system involvement related to Twinkle gene mutation is limited. We present a new French family of whom two members displayed myopathy and neuropathy associated with PEO, and we perform a clinical review in light of other observations reported in the literature. METHODS: The proband, one son and the daughter have been investigated. Southern blot analysis and long-range PCR assay have been performed from muscle biopsy specimens. Coding exons and flanking intron regions of polymerase gamma (POLG) and DNA helicase (Twinkle) genes were sequenced. RESULTS: Multiple mitochondrial DNA deletions have been found and sequencing of the Twinkle gene showed the change p.R374Q. CONCLUSION: Two other families from the literature also had the R374Q mutation. Symptoms reported in association with this mutation were myopathy, peripheral neuropathy, dysarthria and/or dysphagia, respiratory insufficiency and parkinsonism. Respiratory insufficiency caused by chest wall weakness was reported in other families with different Twinkle gene mutations, and one might provide exercise intolerance, dysarthria and/or dysphagia as symptoms in favor of the diagnosis. Occurrence of impressive emaciation was a peculiarity in our family.


Subject(s)
DNA Helicases/genetics , Mutation , Ophthalmoplegia, Chronic Progressive External/genetics , Biopsy , Blotting, Southern , DNA, Mitochondrial/genetics , Female , France , Humans , Male , Middle Aged , Mitochondrial Proteins , Muscle, Skeletal/pathology , Ophthalmoplegia, Chronic Progressive External/pathology , Ophthalmoplegia, Chronic Progressive External/physiopathology , Pedigree , Polymerase Chain Reaction , Young Adult
18.
Rev Neurol (Paris) ; 166(5): 502-8, 2010 May.
Article in French | MEDLINE | ID: mdl-20044116

ABSTRACT

BACKGROUND: Limb girdle muscular dystrophies are rare genetic diseases. Despite constant progress in genetics and biochemistry, the pathogenic mechanisms are not completely understood. Calpainopathy (LGMD2A) has been reported to be the most frequent autosomal recessive form of muscular dystrophy in several populations. Point mutations in CAPN3 are difficult to identify and the analysis is long and costly. The use of western blot does not seem to provide the expected sensitivity and specificity. PATIENTS AND METHOD: We studied all the patients diagnosed in the neuromuscular center of Bordeaux (France) with confirmed calpainopathy in order to establish the appropriate diagnostic approach (inclusion criteria: muscular biopsy with calpain 3 western blot study, two mutations in CAPN3). Patients with highly suspected calpainopathy (same criteria with only one mutation) were also analyzed. RESULTS: Our 13 patients belonged to 10 different families. Four patients had a normal western blot for calpain (WBn). We found high phenotypic variability with frequent atypical signs. The WBn group had less severe disease (a statistically significant later age of onset, a tendency toward lower CK levels and a slower disease course). We extended this comparison to the single mutation patients and we found the same results. CONCLUSION: Considering the lack of sensitivity of western blot protein analysis in LGMD2A, a normal western blot for calpain should not halt the genetic analysis. The western blot result seems to have prognostic value. A normal western blot may help genetic testing by highlighting some mutational hot spots in the CAPN3 gene.


Subject(s)
Calpain/physiology , Muscular Dystrophies, Limb-Girdle/diagnosis , Adolescent , Adult , Age of Onset , Blotting, Western , Calpain/genetics , Child , Cohort Studies , Disability Evaluation , Disease Progression , Female , Humans , Male , Middle Aged , Muscle Proteins/genetics , Neuromuscular Diseases/diagnosis , Phenotype , Point Mutation , Prognosis , Young Adult
19.
J Neurol Neurosurg Psychiatry ; 80(12): 1394-8, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19917821

ABSTRACT

Bilateral periventricular nodular heterotopia (BPNH) is the most common form of periventricular heterotopia. Mutations in FLNA, encoding filamin A, are responsible for the X linked dominant form of BPNH (FLNA-BPNH). Recently, atypical phenotypes including BPNH with Ehlers-Danlos syndrome (BPNH-EDS) have been recognised. A total of 44 FLNA mutations have so far been reported in this phenotype. Most of these mutations lead to a truncated protein, but few missense mutations have also been described. Here, the results of a mutation screening conducted in a series of 32 BPNH patients with the identification of 12 novel point mutations in 15 patients are reported. Nine mutations were truncating, while three were missense. Three additional patients with BPNH-EDS and a mutation in FLNA are described. No phenotype-genotype correlations could be established, but these clinical data sustain the importance of cardiovascular monitoring in FLNA-BPNH patients.


Subject(s)
Contractile Proteins/genetics , Microfilament Proteins/genetics , Periventricular Nodular Heterotopia/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Filamins , France , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Mutation, Missense/genetics , Phenotype , Point Mutation/genetics , Young Adult
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