Publications by authors named "Tanya Stojkovic"

Congenital titinopathies reported to date show autosomal recessive inheritance and are caused by a variety of genomic variants, most of them located in metatranscript (MTT)-only exons. The aim of this study was to describe additional patients and establish robust genotype-phenotype associations in titinopathies. This study involved analyzing molecular, clinical, pathological, and muscle imaging features in 20 patients who had at least one pathogenic or likely pathogenic variant in MTT-only exons, with onset occurring antenatally or in the early postnatal stages.

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  • * Researchers analyzed data from 275 CMTX1 patients across 13 centers in France, finding that those with mutations in transmembrane domains had more severe symptoms and earlier onset than those with mutations in intracellular or extracellular domains.
  • * The findings suggest that the type of genetic mutation not only helps diagnose CMTX1 but also predicts disease severity, emphasizing the need to consider these correlations in upcoming clinical research.
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Background: Myosin heavy chain 7 ()-related myopathies (-RMs) are a group of muscle disorders linked to pathogenic variants in the gene, encoding the slow/beta-cardiac myosin heavy chain, which is highly expressed in skeletal muscle and heart. The phenotype is heterogeneous including distal, predominantly axial or scapuloperoneal myopathies with variable cardiac involvement.

Methods: We retrospectively analysed the clinical, muscle MRI, genetic and myopathological features of 57 patients.

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  • Neurogenetic disorders linked to mutations in spectrin genes lead to a wide range of symptoms, from peripheral nervous system issues to complex syndromes, emphasizing their diverse impact.
  • An international study identified 14 families with unexplained distal weakness due to heterozygous loss-of-function variants, collecting standardized clinical and imaging data to analyze the condition further.
  • The research found that all 20 patients exhibited early childhood onset of distal weakness with varying severity, along with associated foot abnormalities and muscle changes, confirming the link between these genetic variants and a new syndrome characterized by primarily myogenic effects.
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  • The study aimed to broaden the understanding of IMNEPD1, a rare genetic disorder, particularly in patients with neuropathy and pancreatic lipomatosis.
  • Two elderly sisters showed severe neurological symptoms, including sensorimotor neuropathy, hearing loss, and respiratory issues, requiring wheelchairs and ventilation later in life.
  • Genetic analysis revealed a likely pathogenic variant in both sisters, suggesting that testing for this gene is essential for patients with similar gastrointestinal and neurological issues.
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TIA1/SQSTM1 myopathy is one of the few digenic myopathies. We describe four new French adult male patients carrying the TIA1 p.Asn357Ser and SQSTM1 p.

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  • Oculopharyngodistal myopathy (OPDM) is a genetic muscle disease that causes drooping eyelids, trouble swallowing, and weakness in the arms and legs.
  • Recent research found repeating sequences in a gene called ABCD3 in people with OPDM from European backgrounds, while similar repeats were only discovered in certain Asian groups before.
  • These long repeats in the ABCD3 gene might play a role in the muscle problems seen in OPDM, suggesting a link between these repeats and the weakness that affects patients.
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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.

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Background And Aims: Pathogenic variants in the NARS1 gene, which encodes for the asparaginyl-tRNA synthetase1 (NARS1) enzyme, were associated with complex central and peripheral nervous system phenotypes. Recently, Charcot-Marie-Tooth (CMT) disease has been linked to heterozygous pathogenic variants in NARS1 in nine patients. Here, we report two brothers and their mother from a French family with distal hereditary motor neuropathy (dHMN) carrying a previously unreported NARS1 variant.

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  • Congenital myasthenic syndromes (CMS) are genetic disorders that impact neuromuscular transmission, primarily identified in childhood but often diagnosed in adulthood, leading to challenges in management.
  • A study of 235 adult CMS patients in France revealed diverse genetic mutations and highlighted the need for ongoing care, as the prognosis and long-term outcomes remain unclear.
  • The research categorized patients based on the initial symptoms and found varied disease progression patterns, with certain genotypes showing higher rates of ICU admission and the stability of phenotypical features across a patient's life.
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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.

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  • Collagen VI-related dystrophies (COL6-RDs) include a range of conditions such as Ullrich congenital muscular dystrophy (UCMD), which features severe muscle weakness and respiratory issues, and Bethlem muscular dystrophy, which has milder and later-presenting symptoms.
  • Some patients with symptoms typical of COL6-RDs were previously undiagnosed until a deep intronic variant in COL6A1 was identified, leading to a severe form of UCMD in a cohort of 44 patients, except for one with a milder phenotype.
  • The study suggests that a new pseudoexon skipping therapy could effectively reduce the severity of UCMD symptoms by targeting the abnormal transcripts
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Background: Caused by duplications of the gene encoding peripheral myelin protein 22 (PMP22), Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Despite this shared genetic origin, there is considerable variability in clinical severity. It is hypothesized that genetic modifiers contribute to this heterogeneity, the identification of which may reveal novel therapeutic targets.

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Objective: X-linked myopathy with excessive autophagy (XMEA) linked to the VMA21 gene leads to autophagy failure with progressive vacuolation and atrophy of skeletal muscles. Current knowledge of this rare disease is limited. Our objective was to define the clinical, radiological, and natural history of XMEA.

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  • Sodium dependent multivitamin transporter (SMVT) deficiency is a rare genetic disorder that causes health issues due to a lack of certain vitamins, affecting around 10 known families.
  • This study introduced 4 new patients from Algeria, all sharing a specific genetic mutation related to SMVT, confirming its harmful effects through RNA analysis.
  • The patients exhibited similar symptoms, including optic atrophy, severe vomiting, and rapid neurological decline, suggesting a common genetic background due to a "founder effect."
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  • 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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RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat.

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Background: Biallelic intronic AAGGG repeat expansions in the replication factor complex subunit 1 (RFC1) gene were identified as the leading cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome. Patients exhibit significant clinical heterogeneity and variable disease course, but no potential biomarker has been identified to date.

Objectives: In this multicenter cross-sectional study, we aimed to evaluate neurofilament light (NfL) chain serum levels in a cohort of RFC1 disease patients and to correlate NfL serum concentrations with clinical phenotype and disease severity.

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Background And Objectives: Pathogenic variants in the valosin-containing protein () gene cause a phenotypically heterogeneous disorder that includes myopathy, motor neuron disease, Paget disease of the bone, frontotemporal dementia, and parkinsonism termed multisystem proteinopathy. This hallmark pleiotropy makes the classification of novel variants challenging. This retrospective study describes and assesses the effect of 19 novel or nonpreviously clinically characterized variants identified in 28 patients (26 unrelated families) in the retrospective VCP International Multicenter Study.

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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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