Phenotypic Variability of LGMD 2C/R5 in a Genetically Homogenous Group of Bulgarian Muslim Roma.

Sarcoglycanopathies are among the most frequent and severe forms of autosomal recessive forms of limb-girdle muscular dystrophies (LGMDs) with childhood onset. Four subtypes are known: LGMDR3, LGMDR4, LGMDR5 and LGMDR6, which are caused, respectively, by mutations in the , SGCB, and genes. We present the clinical variability of LGMD 2C/R5 among a genetically homogeneous group of 57 patients, belonging to 35 pedigrees.

Identification and Characterization of Novel Founder Mutations in : Refining the Genetic Landscape of Charcot-Marie-Tooth Disease Type 4D in Bulgaria.

Charcot-Marie-Tooth neuropathy type 4D (CMT4D) is a rare genetic disorder of the peripheral nervous system caused by biallelic mutations in the N-Myc Downstream Regulated 1 gene (). Patients present with an early onset demyelinating peripheral neuropathy causing severe distal muscle weakness and sensory loss, leading to loss of ambulation and progressive sensorineural hearing loss. The disorder was initially described in the Roma community due to a common founder mutation, and only a handful of disease-causing variants have been described in this gene so far.

Clinical and genetic variability among Bulgarian patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Background: Autosomal recessive spastic ataxia ofCharlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterizedby early-onset cerebellar ataxia, peripheral sensorimotor neuropathy, and lowerlimb spasticity. We present clinical andgenetic data of the first Bulgarian patients diagnosed with ARSACS by wholeexome sequencing (WES).

Methods: Variant filtering was performed usinglocally established pipeline and the selected variants were analysed by Sangersequencing.

Essential components of an effective transition from paediatric to adult neurologist care for adolescents with Duchenne muscular dystrophy; a consensus derived using the Delphi methodology in Eastern Europe, Greece and Israel.

Purpose: An increasing number of patients with Duchenne muscular dystrophy (DMD) now have access to improved standard of care and disease modifying treatments, which improve the clinical course of DMD and extend life expectancy beyond 30 years of age. A key issue for adolescent DMD patients is the transition from paediatric- to adult-oriented healthcare. Adolescents and adults with DMD have unique but highly complex healthcare needs associated with long-term steroid use, orthopaedic, respiratory, cardiac, psychological, and gastrointestinal problems meaning that a comprehensive transition process is required.

Advancing the Understanding of Vesicle-Associated Membrane Protein 1-Related Congenital Myasthenic Syndrome: Phenotypic Insights, Favorable Response to 3,4-Diaminopyridine, and Clinical Characterization of Five New Cases.

Background: Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular junction (NMJ) disorders arising from gene variants encoding diverse NMJ proteins. Recently, the VAMP1 gene, responsible for encoding the vesicle-associated membrane protein 1 (VAMP1), has been associated with CMS.

Methods: This study presents a characterization of five new individuals with VAMP1-related CMS, providing insights into the phenotype.

Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes.

Exploring the molecular basis of disease severity in rare disease scenarios is a challenging task provided the limitations on data availability. Causative genes have been described for Congenital Myasthenic Syndromes (CMS), a group of diverse minority neuromuscular junction (NMJ) disorders; yet a molecular explanation for the phenotypic severity differences remains unclear. Here, we present a workflow to explore the functional relationships between CMS causal genes and altered genes from each patient, based on multilayer network community detection analysis of complementary biomedical information provided by relevant data sources, namely protein-protein interactions, pathways and metabolomics.

Case Report: Transthyretin Glu54Leu-a rare mutation with predominant cardiac phenotype.

We report two unrelated Bulgarian families with hereditary transthyretin (ATTR) amyloidosis due to a rare p.Glu74Leu (Glu54Leu) pathogenic variant found in seven individuals-three of them symptomatic. Only one family with the same variant and with a Swedish origin has been clinically described so far.

Real-world effectiveness of fingolimod in patients with multiple sclerosis in Bulgaria.

Introduction: Fingolimod, a sphingosine-1-phosphate receptor agonist used for the treatment of multiple sclerosis (MS). Our goal was to assess the impact of fingolimod on quality of life in patients with relapsing-remitting multiple sclerosis (RRMS) after 2 years of treatment in this real-world study.

Patients And Methods: This was a 2-year, prospective, observational study conducted in Bulgaria in RRMS patients treated with fingolimod.

Navigating the ALS Genetic Labyrinth: The Role of MAPT Haplotypes.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by wide clinical and biological heterogeneity, with a large proportion of ALS patients also exhibiting frontotemporal dementia (FTD) spectrum symptoms. This project aimed to characterize risk subtypes of the H1 haplotype within the (microtubule-associated protein tau) gene, according to their possible effect as a risk factor and as a modifying factor in relation to the age of disease onset. One hundred patients from Bulgaria with sporadic ALS were genotyped for the variants rs1467967, rs242557, rs1800547, rs3785883, rs2471738, and rs7521.

Variation of tafamidis plasma levels during the treatment of TTR amyloidosis patients with Glu89Gln mutation.

Purpose: The transthyretin kinetic stabilizer tafamidis, used as a first-line therapy of amyloidosis patients, binds selectively to the transthyretin protein structure and thus prevents its dissociation. The limited information regarding tafamidis application in Glu89Gln amyloidosis patients imposed our research team to determine and evaluate its individual mean plasma levels and their biological variation.

Methods: The present cohort study investigated Bulgarian amyloidosis patients, grouped by gender, age, and therapy duration.

Tyrosyl-tRNA synthetase has a noncanonical function in actin bundling.

Dominant mutations in tyrosyl-tRNA synthetase (YARS1) and six other tRNA ligases cause Charcot-Marie-Tooth peripheral neuropathy (CMT). Loss of aminoacylation is not required for their pathogenicity, suggesting a gain-of-function disease mechanism. By an unbiased genetic screen in Drosophila, we link YARS1 dysfunction to actin cytoskeleton organization.

Novel variant c.92T > G (p.Val31Gly) in the gene (ALS18) responsible for a specific phenotype in a large Bulgarian amyotrophic lateral sclerosis pedigree.

Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive deterioration of motor function, disability, and death. Variants in the gene, encoding the Profilin-1 protein, are related to ALS18.

Methods: We present a pedigree consisting of 3 generations and 4 affected individuals, 3 of which carry a novel heterozygous variant: c.

Arginase deficiency in Bulgaria: first cases and potential endemic region for the disorder.

Arginase deficiency is an autosomal recessive urea cycle disorder caused by pathogenic variants in the gene. The clinical features of the disease include spasticity, tremour, ataxia, hypotonia, microcephaly and seizures. Growth delay can also be observed in the affected individuals.

Telemedicine in Neuromuscular Diseases During Covid-19 Pandemic: ERN-NMD European Survey.

Background: Telemedicine (TM) contributes to bridge the gap between healthcare facilities and patients' homes with neuromuscular disease (NMD) because of mobility issues. However, its deployment is limited due to difficulties evaluating subtle neurological signs such as mild weakness or sensory deficits. The COVID-19 pandemic has disrupted healthcare delivery worldwide, necessitating rapid measures implementation by health care providers (HCPs) to protect patients from acquiring SARS-CoV-2 while maintaining the best care and treatment.

Seven Years of Selective Genetic Screening Program and Follow-Up of Asymptomatic Carriers With Hereditary Transthyretin Amyloidosis in Bulgaria.

Unlabelled: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a rare, autosomal-dominant (AD) multisystem disorder resulting from the extracellular deposition of amyloid fibrils formed by a destabilized mutant form of transthyretin (TTR), a transport protein predominantly produced by the liver.

Aim: The aims of the current study are to demonstrate the Bulgarian experience with the screening programs among the high-risk patient population over the last 7 years, to present the results from the therapy with TTR stabilizer in our cohort, as well as to stress on the importance of a follow-up of asymptomatic carriers with TTR pathogenic variants by a multidisciplinary team of specialists.

Materials And Methods: In 2014, a screening program among the high-risk patient population for ATTRv was initiated in Bulgaria.

Determination of Tafamidis Plasma Concentrations in Amyloidosis Patients with Glu89Gln Mutation by HPLC-UV Detection.

Present study describes a high-performance liquid chromatography method for the determination of the potent kinetic stabilizer-Tafamidis in human plasma. It was approved for medical use in European Union in 2011. Ultra violet (UV) detection mode and isocratic elution of the mobile phase were set and made the analytical procedure fast and widely applicable.

Screening for hereditary transthyretin amyloidosis in Bulgaria.

Transthyretin amyloid (ATTR) amyloidosis is a rare disorder with an adult-onset defined by the accumulation of misfolded fibrils predominantly in peripheral nerves, the heart, and the digestive tract. The disease is characterized by two forms - hereditary (ATTRv) or acquired (ATTRwt). Various point mutations in the transthyretin gene induce the hereditary form of the disease.