Publications by authors named "Anne Laure Bedat-Millet"

Background: Spinal muscular atrophy (SMA) patients benefit from pre-mRNA splicing modifiers targeting the SMN2 gene, which aims to increase functional SMN production. The animal toxicity affecting spermatogenesis associated with one such treatment raised questions about male SMA patients' spermatogenesis.

Methods: This descriptive, cross-sectional study was conducted from June 2022 to July 2023.

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Article Synopsis
  • In 2017, nusinersen, an injectable treatment for spinal muscular atrophy (SMA), was introduced, followed by the oral treatment risdiplam in 2020, leading to questions about appropriate care for adults with SMA due to limited data.
  • To standardize treatment access in France, a national SMA multidisciplinary team meeting (SMDT) was established in 2018 to support decision-making for adult patients.
  • An analysis of 107 patient cases showed that the SMDTs provided various treatment recommendations based on consultations, with most requests aimed at starting new treatments (nusinersen or risdiplam).
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  • * The majority of the 44 patients experienced disease onset during childhood, with symptoms including muscle pain, weakness, and frequent episodes of rhabdomyolysis, often leading to significant complications; many patients took years to receive a diagnosis.
  • * The study suggests the establishment of a standardized patient registry to better track and evaluate treatment effectiveness and patient outcomes over the long term.
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  • This study focuses on non-5q spinal muscular atrophy (SMA), aiming to explore its clinical and genetic characteristics and the effectiveness of gene panels for diagnosis.
  • The research included 71 patients from various centers who underwent genetic testing, revealing a lower diagnostic success rate in those with specific types of SMA symptoms, and highlighting factors that could predict a successful diagnosis.
  • The findings indicate that while neuropathy gene panels provide some insights (about 32% success), broader genetic testing is necessary to enhance understanding and treatment for patients with this genetically diverse condition.
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  • The French Pompe Disease Registry was established in 2004 to track the progress of the disease in patients and evaluate the long-term effects of enzyme replacement therapy (ERT) with alglucosidase-alfa.
  • An update on 210 patients from the registry reveals that the median age of participants was almost 49, with many initially presenting symptoms like muscle weakness and respiratory issues, affecting their mobility significantly.
  • The findings indicate that awareness among doctors has improved, leading to earlier diagnoses and a decrease in the severity of cases at the time of inclusion, highlighting the registry's role in understanding and managing Pompe disease effectively.
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Background And Purpose: Biallelic variants in SORD have been reported as one of the main recessive causes for hereditary peripheral neuropathies such as Charcot-Marie-Tooth disease type 2 (CMT2) and distal hereditary motor neuropathy (dHMN) resulting in lower limb (LL) weakness and muscular atrophy. In this study, phenotype and genotype landscapes of SORD-related peripheral neuropathies were described in a French and Swiss cohort. Serum sorbitol dosages were used to classify SORD variants.

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Muscle phosphorylase kinase b deficiency (PhK) is a rare disorder of glycogen metabolism characterized by exercise-induced myalgia and cramps, myoglobinuria and progressive muscle weakness. PhK deficiency is due to mutations in the PHKA1 gene inherited in an X-linked manner and is associated to glycogenosis type VIII (GSD VIII also called GSD IXd). PHKA1 gene codes for the αM subunit of the PhK, a multimeric protein complex responsible for the control of glycogen breakdown in muscle.

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Background: To describe the clinical, pathological, and molecular characteristics of late-onset (LO) dysferlinopathy patients.

Methods: Retrospective series of patients with LO dysferlinopathy, defined by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early-onset (EO) dysferlinopathy (<30 years) were randomly selected from the COS study as a control group, and the North Star Assessment for Dysferlinopathy (NSAD) and Activity Limitation (ACTIVLIM) scores were used to assess functionality.

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Fingerprint bodies are observed in a variety of clinical situations with no definite genetic cause identified so far. We report for the first time the association of fingerprint bodies with rods in a patient who developed a slowly progressive myopathy affecting the face and limb extremities. Ultrastructural examination first disclosed fingerprint bodies and on a second biopsy, associated cytoplasmic bodies and rods.

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Objectives: We conducted a retrospective study to characterize the cardiac complications in patients with genetically confirmed type 1 facioscapulohumeral dystrophy.

Methods: We reviewed baseline cardiac investigations, including electrocardiogram, Holter electrocardiogram and echocardiogram, as well as cardiac complications that occurred during follow-up in 56 adult patients (37 men, mean duration of disease: 20 years).

Results: Baseline evaluation revealed minor cardiac anomalies in 23 patients including incomplete right bundle branch block (iRBBB) in 13 patients (23%).

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STIM1 is a reticular Ca sensor composed of a luminal and a cytosolic domain. Missense mutations in the luminal domain have been associated with tubular aggregate myopathy (TAM), while cytosolic mutations can cause Stormorken syndrome, a multisystemic disease associating TAM with asplenia, thrombocytopenia, miosis, ichthyosis, short stature and dyslexia. Here we present the case of a 41-year-old female complaining of exercise intolerance.

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Myasthenia gravis (MG) with antibodies against muscle-specific tyrosine kinase (MuSK) is a rare disorder of neuromuscular transmission affecting preferentially bulbar, neck and respiratory muscles. We report the case of a 22-year-old man who presented with diplopia on lateral gaze to both sides, facial diplegia, nasal dysarthria and dysphagia. Repetitive nerve stimulation of the trapezius and orbicularis oculi muscles showed amplitude decrements of 19% and 41% respectively supporting the diagnosis of myasthenia gravis.

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Background: Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported.

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Objective: To report that homoplasmic deleterious mutations in the mitochondrial DNA MT-ATP6/8 genes may be responsible for acute episodes of limb weakness mimicking periodic paralysis due to channelopathies and dramatically responding to acetazolamide.

Methods: Mitochondrial DNA sequencing and restriction PCR, oxidative phosphorylation functional assays, reactive oxygen species metabolism, and patch-clamp technique in cultured skin fibroblasts.

Results: Occurrence of a typical MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome in a single member of a large pedigree with episodic weakness associated with a later-onset distal motor neuropathy led to the disclosure of 2 deleterious mitochondrial DNA mutations.

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We described the case of a patient with recurrent episodes of isolated diplopia over the last 30 years. On her last event, neurological examination revealed not only a right third and sixth cranial nerves involvement, but also a right peripheral facial palsy and a motor weakness on the left ulnar territory. Electrophysiological nerves motor conduction study revealed a conduction block on the left ulnar nerve and a less severe on the right ulnar nerve.

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We report the case of a 71-year-old woman with typical signs of bulbar amyotrophic lateral sclerosis (ALS) associated with immunoglobulin M (IgM) monoclonal gammopathy and anti-MAG (myelin-associated glycoprotein) antibodies. This unusual association between ALS and anti-MAG antibodies has previously been reported in a single case. Our present case, at neuropathological examination, demonstrated no causative link between anti-MAG antibodies and ALS.

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Article Synopsis
  • VLCAD deficiency is a genetic condition affecting the body's ability to oxidize long-chain fatty acids, often seen in children but can also affect adults, leading to exercise intolerance and rhabdomyolysis.
  • The study analyzes 13 adult patients, revealing symptoms typically triggered by exercise, fasting, cold, or fever, with many reporting serious health issues before age 3.
  • Biochemical tests showed elevated long-chain acylcarnitines, and genetic analysis identified specific mutations in most patients, highlighting the need for VLCAD deficiency to be included in diagnoses of exercise-induced muscle issues.
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