Genetic analysis of GBA1 gene in a cohort of patients with Parkinson's disease.

Background: Variants in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are among the strongest genetic risk factors for Parkinson's disease (PD). While several pathogenic mutations are well-characterized, the impact of many rare or novel variants remains unclear.

Objective: This study is aimed to explore the spectrum of GBA1 variants in a cohort of PD patients from Southern Italy, with a particular focus on the clinical and structural characterization of a novel missense variant through integrated genetic and in silico analyses.

Subhaplotypes in Different Progressive Supranuclear Palsy Phenotypes.

Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder characterized by abnormal tau protein aggregation. The gene encodes for tau protein. The locus harbors two major haplotypes, H1 and H2, with H1 and its subhaplotypes being associated with an increased risk of PSP.

Identification of Ser71Arg mutation in RAB32 gene in familial Parkinson's disease from Southern Italy.

We identified the RAB32 c.213 C > G variant in 7/300 unrelated familial PD patients (not found in 300 controls) from Southern Italy, screened by Sanger sequencing. We found a prevalence of 2.

Novel Variants Related to a Variable Phenotypic Spectrum Ranging from Epilepsy with Auditory Features to Severe Developmental and Epileptic Encephalopathies.

Pathogenic variants are associated with neonatal epilepsies, ranging from self-limited neonatal epilepsy to -developmental and epileptic encephalopathy (DEE). In this study, next-generation sequencing was performed, applying a panel of 142 epilepsy genes on three unrelated individuals and affected family members, showing a wide variability in the epileptic spectrum. The genetic analysis revealed two likely pathogenic missense variants (c.

National survey on the prevalence of single-gene aetiologies for genetic developmental and epileptic encephalopathies in Italy.

Background: We aimed to estimate real-world evidence of the prevalence rate of genetic developmental and epileptic encephalopathies (DEEs) in the Italian population over a 11-year period.

Methods: Fifteen paediatric and adult tertiary Italian epilepsy centres participated in a survey related to 98 genes included in the molecular diagnostic workflows of most centres. We included patients with a clinical diagnosis of DEE, caused by a pathogenic or likely pathogenic variant in one of the selected genes, with a molecular diagnosis established between 2012 and 2022.

Two Novel Variants in the and Genes in Italian Patients with Febrile Seizures.

Background: Febrile seizures (FSs) are the most common form of epilepsy in children aged between six months and five years. The exact cause is unknown, but several studies have demonstrated the importance of genetic predisposition, with increasing involvement of receptors and ion channels. The present study aims to identify novel pathogenic variants in Italian patients with FSs.

Phenotypic Variability in Novel Doublecortin Gene Variants Associated with Subcortical Band Heterotopia.

Doublecortin, encoded by the gene, plays a crucial role in the neuronal migration process during brain development. Pathogenic variants of the gene are the major causes of the "lissencephaly (LIS) spectrum", which comprehends a milder phenotype like Subcortical Band Heterotopia (SBH) in heterozygous female subjects. We performed targeted sequencing in three unrelated female cases with SBH.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

ANXA1 mutation analysis in Italian patients with early onset PD.

Recently, a novel pathogenic variant in Annexin A1 protein (c.4G > A, p.Ala2Thr) has been identified in an Iranian consanguineous family with autosomal recessive parkinsonism.

Neurological manifestations in patients and disease carriers in an Italian family with osteosclerosis.

Background: Hereditary cranial hyperostosis is a rare disease never described in Italy, so the neurological manifestations in patients and carriers of the disease have been little studied.

Methods: We describe the neurological and neuroimaging features of patients and carriers of the gene from a large Italian family with sclerosteosis.

Results: In this family, genetic testing detected the homozygous p.

Multiple system atrophy and C9orf72 hexanucleotide repeat expansions in a cohort of Italian patients.

Exanucleotide expansions in C9orf72 gene have been described as potential risk factor in some patients with Multiple system atrophy (MSA) and other forms of atypical parkinsonism. The goal of our study was to extend the knowledge on the involvement of C9orf72 in MSA studying a cohort of 100 patients from Italy. We identified 2 heterozygous patients in the pathological range (> 30 repeats) and 4 heterozygous patients for expansions in the premutation range (20 -30 repeats).

Exome-wide association study of levodopa-induced dyskinesia in Parkinson's disease.

Levodopa is the standard long-term dopamine replacement therapy to treat Parkinson's disease (PD) symptoms. With time, levodopa may induce debilitating dyskinesias (LID), the treatment of which represents a large clinically unmet need. However, time-to-LID onset varies between patients, reflecting a possible genetic component.

Aceruloplasminemia: a multimodal imaging study in an Italian family with a novel mutation.

Objective: Structural abnormalities in thalami and basal ganglia, in particular the globus pallidus (GP), are a neuroimaging hallmark of hereditary aceruloplasminemia (HA), yet few functional imaging data exit in HA carriers. This study investigated the iron-related structural and functional abnormalities in an Italian HA family.

Methods: Multimodal imaging was used including structural 3 T MRI, functional imaging (SPECT imaging with I-ioflupane (DAT-SPECT), cardiac I metaiodobenzylguanidine (I-MIBG) scintigraphy, and F-fluorodeoxyglucose (F-FDG)-PET imaging).

Analysis of the LRP10 gene in patients with Parkinson's disease and dementia with Lewy bodies from Southern Italy.

Recently, the LRP10 gene has been associated with Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB). The aim of the present study was to evaluate the presence of mutations of the LRP10 gene in patients with PD or DLB from Southern Italy. Sequencing analysis revealed only 2 missense and 3 synonymous variants in patients and control subjects and a rare variant p.