Structural variation in nebulin and its implications on phenotype and inheritance: establishing a dominant distal phenotype caused by large deletions.

Introduction: Structural variants (SVs) of the nebulin gene (), including intragenic duplications, deletions, and copy number variation of the triplicate region, are an established cause of recessively inherited nemaline myopathies and related neuromuscular disorders. Large deletions have been shown to cause dominantly inherited distal myopathies. Here we provide an overview of 35 families with muscle disorders caused by such SVs in .

Minimal invasive biopsies are highly sensitive for amyloid detection in hereditary transthyretin amyloidosis with polyneuropathy.

Objective: To assess the effectiveness of labial minor salivary gland biopsy (LSGB) alone or in combination with punch skin biopsy (SB) for the detection of amyloid deposits in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).

Methods: In this single-center retrospective study, Congo red staining of minimal invasive LSGB (4 mm) and SB (3 mm) was assessed in ATTRv-PN patients consecutively evaluated between 2012 and 2023.

Results: Histopathological data of 171 ATTRv-PN, including 49 early-onset p.

Tracking myasthenia gravis severity over time: Insights from the French health insurance claims database.

Background And Purpose: Few data are available on the course of myasthenia gravis (MG) regarding disease severity and stability over time in real-world settings. This study used the French National Health Insurance Database (SNDS) to assess markers of disease severity in patients with MG longitudinally.

Methods: All patients with MG-related claims in the SNDS between 2013 and 2020 were identified.

Nonamyloidogenic TTR gene variants c.76G>A and c.337-18G>C are not associated with idiopathic small-fiber neuropathy.

Background And Purpose: Small-fiber neuropathy (SFN) affects only unmyelinated and thin myelinated fibers. It may be caused by amyloidogenic mutations of the transthyretin (TTR) gene, but not all TTR gene variants are pathogenic. The nonamyloidogenic c.

French National Protocol for diagnosis and care of facioscapulohumeral muscular dystrophy (FSHD).

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common genetically inherited myopathies in adults. It is characterized by incomplete penetrance and variable expressivity. Typically, FSHD patients display asymmetric weakness of facial, scapular, and humeral muscles that may progress to other muscle groups, particularly the abdominal and lower limb muscles.

The 5'-UTR Mutation in Charcot-Marie-Tooth 4G Disease Alters Hexokinase 1 Binding to Voltage-Dependent Anion Channel-1 and Leads to Dysfunctional Mitochondrial Calcium Buffering.

Demyelinating Charcot-Marie-Tooth 4G (CMT4G) results from a recessive mutation in the 5'UTR region of the Hexokinase 1 (HK1) gene. HK participates in mitochondrial calcium homeostasis by binding to the Voltage-Dependent Anion Channel (VDAC), through its N-terminal porin-binding domain. Our hypothesis is that CMT4G mutation results in a broken interaction between mutant HK1 and VDAC, disturbing mitochondrial calcium homeostasis.

Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

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.

Detailed clinical, physiological and pathological phenotyping can impact access to disease-modifying treatments in ATTR carriers.

Background: Hereditary transthyretin amyloidosis is a life-threatening autosomal dominant systemic disease due to pathogenic variants (ATTRv), mostly affecting the peripheral nerves and heart. The disease is characterised by a combination of symptoms, organ involvement and histological amyloid deposition. The available disease-modifying ATTRv treatments (DMTs) are more effective if initiated early.

Hereditary transthyretin amyloid neuropathies: advances in pathophysiology, biomarkers, and treatment.

Hereditary transthyretin (TTR) amyloid polyneuropathy is an autosomal dominant life-threatening disorder. TTR is produced mainly by the liver but also by the choroid plexus and retinal pigment epithelium. Detailed clinical characterisation, identification of clinical red flags for misdiagnosis, and use of biomarkers enable early diagnosis and treatment.

Hereditary transthyretin amyloidosis in the era of RNA interference, antisense oligonucleotide, and CRISPR-Cas9 treatments.

Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant adult-onset disorder caused by point mutations in the transthyretin (TTR) gene encoding TTR, also known as prealbumin. ATTRv survival ranges from 3 to 10 years, and peripheral nervous system and heart are usually the 2 main tissues affected, although central nervous system and eye may also be involved. Because the liver is the main TTR protein secretor organ, it has been the main target of treatments developed these last years, including liver transplantation, which has been shown to significantly increase survival in a subset of patients carrying the so-called "early-onset Val30Met" TTR gene mutation.

Myasthenia gravis treatment in the elderly presents with a significant iatrogenic risk: a multicentric retrospective study.

Background: Myasthenia gravis (MG) is an autoimmune disease treated with acetylcholinesterase inhibitors and immunosuppressant/immunomodulatory drugs. MG is frequently diagnosed in elderly patients, a fragile population in which treatment adverse effects (TAE) have not been evaluated until now.

Methods: We retrospectively analysed the files of all MG patients with disease onset after age 70 years in four French University Hospitals, including clinical, electrophysiological, biological, and treatment data, with an emphasis on TAE.

Clinical and electrophysiological characteristics of women with X-linked Charcot-Marie-Tooth disease.

Background: X-Linked Charcot-Marie-Tooth disease type 1 (CMTX1) is characterized by gender differences in clinical severity. Women are usually clinically affected later and less severely than men. However, their clinical presentation appears to be heterogenous.

Red Flags for Chronic Inflammatory Demyelinating Polyradiculoneuropathy Associated with Sarcoidosis or Connective Tissue Diseases.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare autoimmune disorder of the peripheral nervous system. Diagnosis relies on clinical and electrophysiological criteria. Various disorders requiring specific treatment regimens may be associated with CIDP, including sarcoidosis (SAR-CIDP) and connective tissue disease (CTD-CIDP).

Comparison between tafamidis and liver transplantation as first-line therapy for hereditary transthyretin amyloidosis.

Background: By stabilizing transthyretin, tafamidis delays progression of amyloidosis due to transthyretin variant (ATTRv) and replaced liver transplantation (LT) as the first-line therapy. No study compared these two therapeutic strategies.

Methods: In a monocentric retrospective cohort analysis, patients with ATTRv amyloidosis treated with either tafamidis or LT were compared using a propensity score and a competing risk analysis for three endpoints: all-cause mortality, cardiac worsening (heart failure or cardiovascular death) and neurological worsening (worsening in PolyNeuropathy Disability score).

French recommendations for the management of adult & pediatric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare autoimmune disorder of the peripheral nervous system, primarily affecting the myelin sheath. The pathophysiology of CIDP is complex, involving both humoral and cellular immunity. The diagnosis of CIDP should be suspected in patients with symmetrical proximal and distal motor weakness and distal sensory symptoms of progressive onset, associated with decreased/abolished tendon reflexes.

Anti-disialosyl-immunoglobulin M chronic autoimmune neuropathies: a nationwide multicenter retrospective study.

Background And Purpose: In this retrospective study involving 14 university hospitals from France and Switzerland, the aim was to define the clinicopathological features of chronic neuropathies with anti-disialosyl ganglioside immunoglobulin M (IgM) antibodies (CNDA).

Results: Fifty-five patients with a polyneuropathy evolving for more than 2 months and with at least one anti-disialosyl ganglioside IgM antibody, that is, anti-GD1b, -GT1b, -GQ1b, -GT1a, -GD2 and -GD3, were identified. Seventy-eight percent of patients were male, mean age at disease onset was 55 years (30-76) and disease onset was progressive (82%) or acute (18%).