Clinical Manifestations.

Background: Valosin Containing Protein (VCP) mutations are responsible some genetic etiologies of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Method: A 67-year-old, male patient, applied to the clinic due to behavioral changes and difficulty swallowing. According the patient history it was reported that his first complaint started 6 years ago (at the age of 61).

The First Case of Autosomal Recessive Cerebellar Ataxia with Prominent Paroxysmal Non-kinesigenic Dyskinesia Caused by a Truncating FGF14 Variant in a Turkish Patient.

Background: ATX-FGF/SCA27A has been exclusively associated with heterozygous variants in the FGF14 gene, presenting with postural tremor, slowly progressive cerebellar ataxia, and psychiatric and behavioral disturbances.

Objectives: This study describes the first case of ATX-FGF/SCA27A linked to a biallelic frameshift variant in the FGF14 gene.

Methods: Whole-exome sequencing (WES) was conducted using the Illumina NovaSeq 6000 platform, and the identified variant was confirmed using Sanger sequencing.

variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify as a new gene implicated in PD and childhood neurodegeneration.

Digital Gait Outcomes for Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS): Discriminative, Convergent, and Ecological Validity in a Multicenter Study (PROSPAX).

Background: With treatment trials on the horizon, this study aimed to identify candidate digital-motor gait outcomes for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), capturable by wearable sensors with multicenter validity, and ideally also ecological validity during free walking outside laboratory settings.

Methods: Cross-sectional multicenter study (four centers), with gait assessments in 36 subjects (18 ARSACS patients; 18 controls) using three body-worn sensors (Opal, APDM) in laboratory settings and free walking in public spaces. Sensor gait measures were analyzed for discriminative validity from controls, and for convergent (ie, clinical and patient relevance) validity by correlations with SPRS (primary outcome) and Scale for the Assessment and Rating of Ataxia (SARA), Spastic Paraplegia Rating Scale (SPRS), and activities of daily living subscore of the Friedreich Ataxia Rating Scale (FARS-ADL) (exploratory outcomes).

MRI-ARSACS: An Imaging Index for Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) Identification Based on the Multicenter PROSPAX Study.

Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and hereditary spastic paraplegia type 7 (SPG7) represent the most common genotypes of spastic ataxia (SPAX). To date, their magnetic resonance imaging (MRI) features have only been described qualitatively, and a pure neuroradiological differential diagnosis between these two conditions is difficult to achieve.

Objectives: To test the performance of MRI measures to discriminate between ARSACS and SPG7 (as an index of common SPAX disease).

Successful infliximab treatment in siblings with Netherton syndrome: Unveiling a novel SPINK5 gene variant and literature review.

Netherton syndrome (NS) is a rare autosomal recessive genodermatosis. In this article, we present two siblings with NS who harbour a novel variant in the SPINK5 gene and were treated with infliximab infusions. Both patients exhibited the characteristic clinical triad of NS, and their whole exome sequencing analysis revealed a homozygous variant, c.

Case report: Revealing the rare-a Brody Disease patient from Turkey expanding the phenotype.

Brody Disease is an exceptionally rare, autosomal recessive myopathy attributed to the pathogenic variants in the , which encodes the sarcoplasmic/endoplasmic reticulum Ca (2+) ATPase type 1 protein SERCA1. It was first described by Brody IA in 1969. To date, only thirty-three Brody families with forty-seven patients have been reported in the literature, and the disease prevalence is considered as 1 in 10 million, demonstrating the peculiarity of the disease.

Evaluation of the Hematological and Serum Biochemistry Parameters in the Pre-Symptomatic and Symptomatic Stages of ALS Disease to Support Early Diagnosis and Prognosis.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. Since there are no pathognomonic tests for ALS prognoses; clinical diagnoses of the disease take time and are usually difficult. Prognostic biomarkers are urgently needed for rapid and effective ALS prognoses.

Impact of the Amyotrophic Lateral Sclerosis Disease on the Biomechanical Properties and Oxidative Stress Metabolism of the Lung Tissue Correlated With the Human Mutant SOD1 Protein Accumulation.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, and ALS incidence is increasing worldwide. Patients with ALS have respiratory failure at the disease's end stages, leading to death; thus, the lung is one of the most affected organs during disease progression. Tissue stiffness increases in various lung diseases because of impaired extracellular matrix (ECM) homeostasis leading to tissue damage and dysfunction at the end.

Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and eventual death. ALS has a multifaceted nature affected by many pathological mechanisms, including oxidative stress (also via protein aggregation), mitochondrial dysfunction, glutamate-induced excitotoxicity, apoptosis, neuroinflammation, axonal degeneration, skeletal muscle deterioration and viruses. This complexity is a major obstacle in defeating ALS.

Phenotypical spectrum of SACS variants: Neuromuscular perspective of a complex neurodegenerative disorder.

Objectives: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by the SACS gene variants. Main clinical features include early-onset and progressive cerebellar ataxia, spasticity, sensorimotor polyneuropathy. However, the phenotypic spectrum expanded with the increased availability of next-generation sequencing methods.

LIPAD (LRRK2/Luebeck International Parkinson's Disease) Study Protocol: Deep Phenotyping of an International Genetic Cohort.

Pathogenic variants in the Leucine-rich repeat kinase 2 ( gene are the most common known monogenic cause of Parkinson's disease (PD). -linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions. To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected pathogenic variant carriers, and controls.

Varied phenotypic spectrum presenting of paroxysmal exercise-induced dyskinesia: a Turkish family with SLC2A1 mutation.

Introduction: Paroxysmal exercise-induced dyskinesia (PED) is characterized by repeated episodes of involuntary movement disorders that are typically caused by prolonged walking or running and mostly caused by SLC2A1 gene mutations. Phenotypes vary from focal dystonia, ataxia, tremor, and complex non-kinesigenic movements to other movement disorders in patients with SLC2A1 mutation. Also, SLC2A1 mutations carriers may present with also other phenotypes such as epileptic seizure and migraine.

A rare case of juvenile amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a chronic motor neuron disease characterised by progressive weakness in striated muscles resulting from the destruction of neuronal cells. The term juvenile ALS (JALS) is used for patients whose symptoms start before 25 years of age. JALS may be sporadic or familial.

Assessment of the corticospinal fiber integrity in mirror movement disorder.

Mirror movements are unintended movements occurring on one side of the body that mirror the contralateral voluntary ones. It has been proposed that mirror movements occur due to abnormal decussation of the corticospinal pathways. Using detailed multidisciplinary approach, we aimed to enlighten the detailed mechanism underlying the mirror movements in a case subject who is diagnosed with mirror movements of the hands and we compared the findings with the unaffected control subjects.

Characterization of the c9orf72 GC-rich low complexity sequence in two cohorts of Italian and Turkish ALS cases.

Large expansions of a noncoding GGGGCC repeat in the C9orf72 gene are the main cause of amyotrophic lateral sclerosis (ALS). The GGGGCC repeat is contiguous with another GC-rich region. Recent studies reported a significantly higher frequency of insertions/deletions within the GC-rich region in patients carrying the GGGGCC expansion.

Efficient Prevention of Neurodegenerative Diseases by Depletion of Starvation Response Factor Ataxin-2.

Ataxin-2 (ATXN2) homologs exist in all eukaryotic organisms and may have contributed to their origin. Apart from a role in endocytosis, they are known for global effects on mRNA repair and ribosomal translation. Cell size, protein synthesis, and fat and glycogen storage are repressed by ATXN2 via mTORC1 signaling.