Neurology gene panel

Alzheimer disease (AD) is a common neurodegenerative disease with a late onset. It is critical to identify novel blood-based DNA methylation biomarkers to better understand the extent of the molecular pathways affected in AD. Two sets of blood DNA methylation genetic prediction models developed using different reference panels and modelling strategies were leveraged to evaluate associations of genetically predicted DNA methylation levels with AD risk in 111,326 (46,828 proxy) cases and 677,663 controls. A total of 1,168 cytosine-phosphate-guanine (CpG) sites showed a significant association with AD risk at a false discovery rate (FDR) < 0...

BACKGROUND: Despite accumulating research on the molecular characteristics of meningiomas, no definitive molecularly targeted therapy for these tumors has been established to date. Molecular mechanisms underlying meningioma progression also remain unclear. Comprehensive genetic testing approaches can reveal actionable gene aberrations in meningiomas. However, there is still limited information on whether profiling the molecular status of subsequent recurrent meningiomas could influence the choice of molecular-targeted therapies...

The Class-I histone deacetylases (HDACs) mediate microglial inflammation and neurological dysfunction after traumatic brain injury (TBI). However, whether the individual Class-I HDACs play an indispensable role in TBI pathogenesis remains elusive. HDAC2 has been shown to upregulate pro-inflammatory genes in myeloid cells under brain injuries such as intracerebral hemorrhage, thereby worsening outcomes. Thus, we hypothesized that HDAC2 drives microglia toward a pro-inflammatory neurotoxic phenotype in a murine model of controlled cortical impact (CCI)...

OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are a group of severe, early-onset epilepsies characterised by refractory seizures, developmental delay, or regression and generally poor prognosis. DEE are now known to have an identifiable molecular genetic basis and are usually examined using a gene panel. However, for many patients, the genetic cause has still not been identified. The aims of this study were to identify causal variants for DEE in patients for whom the previous examination with a gene panel did not determine their genetic diagnosis...

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6 , CPLANE1 , and TBCD ...

Slowly progressive neuromuscular symptoms often have a genetic basis. We present the case of a woman in her 40s with gradually progressive symmetrical weakness and respiratory muscle involvement. Extensive investigation found no specific cause. After a novel neuromuscular gene panel became available, we identified a mutation in the MUSK gene (muscle-specific kinase), confirming a diagnosis of congenital myasthenic syndrome. This group of rare disorders are caused by mutations in genes encoding the neuromuscular junction...

Ataxia-Telangiectasia (A-T) is an autosomal recessive multi-system disorder caused by mutations in the ataxia-telangiectasia mutated (ATM) gene, resulting, among other symptoms, in neurological dysfunction. ATM is known to be a master controller of signal transduction for DNA damage response, with additional functions that are poorly understood. CRISPR/Cas9 technology was used to introduce biallelic mutations at selected sites of the ATM gene in human induced pluripotent stem cells (hiPSCs). This panel of hiPSCs with nonsense and missense mutations in ATM can help understand the molecular basis of A-T...

BACKGROUND: Studies of patients with retinitis pigmentosa (RP) have reported an increased prevalence of optic disc drusen (ODD) compared with the ODD prevalence in the general population. The diagnostic gold standard method for identifying ODD is enhanced depth imaging optical coherence tomography (EDI-OCT), but this modality has not previously been used systematically for identifying ODD in patients with RP. This study aimed to estimate the prevalence of ODD in patients with RP using EDI-OCT...

Focal cortical dysplasia type II (FCDII) is the most common cause of drug-resistant focal epilepsy in children. Herein, we performed a deep histopathology-based genotype-phenotype analysis to further elucidate the clinico-pathological and genetic presentation of FCDIIa compared to FCDIIb. Seventeen individuals with histopathologically confirmed diagnosis of FCD ILAE Type II and a pathogenic variant detected in brain derived DNA whole-exome sequencing or mTOR gene panel sequencing were included in this study...

Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous disorder and the phenotypic variability goes far beyond the used clinical stratification parameter. Evidence has emerged that ALS may coexist with distinct neurodegenerative diseases in single cases. We aim to study the clinical features of two familial cases of ALS carriers of two distinct variants harbored in the Optineurin ( OPTN ) gene. We included definite familial ALS followed up in the Department of Neurology of Razi University Hospital, Tunisia, and selected according to Byrne criteria...

Gitelman syndrome (GS) is a rare renal tubulopathy, classically characterized by renal salt wasting and metabolic alkalosis. It is usually an incidental diagnosis, being asymptomatic or with mild symptoms. GS manifesting with acute flaccid paralysis is extremely uncommon. We report a case of GS that mimicked Guillain-Barré syndrome (GBS), manifesting with acute hypokalemic paralysis. A middle-aged male with no known comorbidities presented to our center with paresthesias of all four limbs for one month and progressive, asymmetric limb weakness over the past eight days...

BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), classically presenting as a triad of early-onset cerebellar ataxia, lower extremity spasticity and peripheral neuropathy, is caused by mutations in SACS gene which encodes the protein sacsin. OBJECTIVE: To provide new insight into the occurrence of SACS mutations in South India. METHODS: Patients with three cardinal features of ARSACS-peripheral neuropathy, cerebellar ataxia, and pyramidal tract signs were included...

Chronic fluorosis has been widely investigated for its adverse effects on skeletal and neurological health; however, its impact on reproductive health, especially in females, remains underexplored. In this study, female Sprague-Dawley rats were exposed to different fluoride concentrations (0.75, 50, and 100 mg/L) in their drinking water for six months. Dental fluorosis and increased urinary fluoride content were observed in fluoride-exposed rats, reflecting fluoride accumulation and exposure levels. Chronic fluorosis resulted in reduced ovary organ coefficient, indicating harmful effects on ovarian tissue...

BACKGROUND AND OBJECTIVES: There is an urgent need to identify novel noninvasive biomarkers for Alzheimer disease (AD) diagnosis. Recent advances in blood-based measurements of phosphorylated tau (pTau) species are promising but still insufficient to address clinical needs. Epigenetics has been shown to be helpful to better understand AD pathogenesis. Epigenetic biomarkers have been successfully implemented in other medical disciplines, such as oncology. The objective of this study was to explore the diagnostic accuracy of a blood-based DNA methylation marker panel as a noninvasive tool to identify patients with late-onset Alzheimer compared with age-matched controls...

OBJECTIVE: Childhood epilepsy is a common neurological disorder with a prevalence of 300-600 cases per 100,000 people. It is associated with refractory epilepsies, global developmental delay, and epileptic encephalopathies, causing epileptic syndromes characterized by cognitive and behavioral disorders. METHODS: In this retrospective cohort study, patients with refractory epilepsy and global developmental delay, defined as epileptic encephalopathy, who applied to the Aydın 7Maternity and Children's Hospital Genetic Diagnosis Center and were followed in the pediatric neurology clinic of our hospital, between July 2018 and July 2021, were included...

It is essential to study disorders of the immune system in chronic encephalopathies of various genesis, considering that the mechanisms of brain damage remain unknown in their molecular basis. Among numerous inflammatory mediators, cytokines are particular in regulating immunological interactions. Many factors, including the genetic ones, determine these pro-inflammatory proteins' activity. The aim of study was to study the prevalence of IL1β C3953T gene polymorphism and TNFα G308A gene polymorphism in patients with chronic traumatic encephalopathy (CTE), microvascular ischemic disease of the brain (or cerebral small vessel disease, (SVD)), chronic alcohol-induced encephalopathy (AIE) and postinfectious encephalopathy (PIE), and to evaluate the impact of a particular genotype presence on the occurrence and/or progression of encephalopathy...

PURPOSE/OBJECTIVE(S): Leptomeningeal disease (LMD) is associated with significant neurologic symptomatology, functional decline, and generally, a very poor prognosis. Clinical characteristics of patients with parenchymal brain metastases have limited potential in predicting who will subsequently develop LMD. We hypothesized that genomic alterations may predict which patients with intracranial disease are at highest risk for developing LMD and sought to identify DNA-based genomic alterations among a targeted panel of cancer-related genes that may increase a patient's risk for LMD...

Fahr's disease, or primary familial brain calcification (PFBC), is a rare genetic neurologic disease characterized by abnormal calcification of the basal ganglia, subcortical white matter and cerebellum. Common clinical features include parkinsonism, neuropsychiatric symptoms, and cognitive decline. Genes implicated in Fahr's disease include PDGFB , PDGFRB , SLC20A2 , XPR1 , MYORG , and JAM2 . We present the case of a 51-year-old woman who developed subacute cognitive and behavioral changes primarily affecting frontal-subcortical pathways and parkinsonism in association with extensive bilateral calcifications within the basal ganglia, subcortical white matter, and cerebellum on neuroimaging...

AIM: To differentiate phenotypic features of individuals with CDKL5 deficiency disorder (CDD) from those of individuals with other infantile-onset epilepsies. METHOD: We performed a retrospective cohort study and ascertained individuals with CDD and comparison individuals with infantile-onset epilepsy who had epilepsy gene panel testing. We reviewed records, updated variant classifications, and compared phenotypic features. Wilcoxon rank-sum tests and χ2 or Fisher's exact tests were performed for between-cohort comparisons...

Congenital myasthenic syndromes are a rare group of inherited disorders caused by gene defects associated with the neuromuscular junction and potentially treatable with commonly available medications such as acetylcholinesterase inhibitors and beta2 adrenergic receptor agonists. In this study we identify and genetically characterise the largest cohort of congenital myasthenic syndrome patients from India to date. Clinically suspected patients evaluated in a South Indian hospital between 2014-2019 underwent genetic testing either by standard diagnostic methods of gene panel testing or a two-step method of hotspot screening followed by whole-exome sequencing...