Late onset bipolar disorder and frontotemporal dementia with mutation in progranulin gene: a case report.

Bipolar disorder is a chronic psychiatric illness characterised by fluctuation in mood state, with a relapsing and remitting course. Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous syndrome, with the most frequent phenotype being behavioural variant frontotemporal dementia (bvFTD). Here, we report the case of an Italian male presenting with late-onset bipolar disorder that developed into bvFTD over time, carrying a mutation in the GRN gene.

KCNK18 (TRESK) genetic variants in Italian patients with migraine.

Objectives: To evaluate the prevalence of KCNK18 gene mutations in a dataset of Italian migraineurs, with and without aura, and in healthy controls, and to investigate in silico the functional effects of the mutations.

Background: A role for the KCNK18 gene encoding for TRESK, a member of the family of potassium channel, has been recently suggested in migraine with aura.

Methods: We sequenced the KCNK18 gene in 425 migraineurs (255 with aura and 170 without aura) and 247 healthy controls.

Genetic variants in the NOTCH4 gene influence the clinical features of migraine.

Background: Recent studies suggested an important role for vascular factors in migraine etiopathogenesis. Notch4 belongs to a family of transmembrane receptors that play an important role in vascular development and maintenance. The aim of this study was to test the hypothesis that polymorphisms of the NOTCH4 gene would modify the occurrence and the clinical features of migraine.

SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Objective: There is increasing evidence that common genetic risk factors underlie frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Recently, mutations in the sequestosome 1 (SQSTM1) gene, which encodes p62 protein, have been reported in patients with ALS. P62 is a multifunctional adapter protein mainly involved in selective autophagy, oxidative stress response, and cell signaling pathways.

Proinflammatory cytokine gene polymorphisms and susceptibility to Paget's disease of bone: an association study.

Background: Recent studies suggested that proinflammatory cytokines are involved in the pathophysiology of Paget's disease of bone (PDB). The purpose of this study was to evaluate whether functionally active polymorphisms of the interleukin-1α (IL-1α), interleukin-1β (IL-β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) genes would modify the occurrence and the clinical features of PDB.

Methods: Genomic DNA was extracted from 144 PDB patients and 115 healthy controls.

Evidence for an association between migraine and the hypocretin receptor 1 gene.

The aim of our study was to investigate whether genetic variants in the hypocretin receptor 1 (HCRTR1) gene could modify the occurrence and the clinical features of migraine. Using a case-control strategy we genotyped 384 migraine patients and 259 controls for three SNPs in the HCRTR1 gene. Genotypic and allelic frequencies of the rs2271933 non-synonymous polymorphism resulted different (χ(2)=9.

Association between major mood disorders and the hypocretin receptor 1 gene.

Background: Recent studies suggested a role for hypocretins in the neurobiology of Major Mood Disorders (MMD). The purpose of this study was to investigate hypocretin involvement in MMD evaluating whether particular alleles or genotypes of the hypocretin pathway genes (HCRT, HCRTR1 and HCRTR2) would modify the occurrence and clinical features of the disease.

Methods: We selected for the study 229 MMD patients and 259 healthy age-, sex- and ethnicity-matched controls.

Interleukin-1 cluster gene polymorphisms and aneurysmal subarachnoid hemorrhage.

Background: Emerging data indicate that proinflammatory cytokines may be involved in the pathogenesis of intracranial aneurysms. Interleukin (IL)-1 is a proinflammatory cytokine that plays a pivotal role in both acute and chronic central nervous system injuries.

Objective: To investigate whether select polymorphisms in the IL-1alpha, IL-1beta, and IL-1 receptor antagonist genes are associated with both susceptibility to and clinical characteristics of subarachnoid hemorrhage due to intracranial aneurysm rupture.

SQSTM1 gene analysis and gene-environment interaction in Paget's disease of bone.

Even though SQSTM1 gene mutations have been identified in a consistent number of patients, the etiology of Paget's disease of bone (PDB) remains in part unknown. In this study we analyzed SQSTM1 mutations in 533 of 608 consecutive PDB patients from several regions, including the high-prevalence area of Campania (also characterized by increased severity of PDB, higher number of familial cases, and peculiar phenotypic characteristics as giant cell tumor). Eleven different mutations (Y383X, P387L, P392L, E396X, M401V, M404V, G411S, D423X, G425E, G425R, and A427D) were observed in 34 of 92 (37%) and 43 of 441 (10%) of familial and sporadic PDB patients, respectively.

Cluster headache is associated with the alcohol dehydrogenase 4 (ADH4) gene.

Background/objectives: Alcohol is a well-known trigger factor for cluster headache attacks during the active phases of the disease. The alcohol dehydrogenase (ADH) pathway, which converts alcohol to the toxic substance acetaldehyde, is responsible for most of the alcohol breakdown in the liver. Humans have 7 ADH genes, tightly clustered on chromosome 4q21-q25, that encode different ADH isoforms.

Absence of TARDBP gene mutations in an italian series of patients with frontotemporal lobar degeneration.

Background/aim: Recent studies showed that TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, is a major pathological protein in both sporadic and familial frontotemporal lobar degeneration (FTLD). The aim of this study was to search for mutations of the TARDBP gene in the disease.

Methods: We sequenced the TARDBP gene in 172 unrelated FTLD patients recruited from 2 Italian memory clinics.

Pro-inflammatory cytokine genes influence the clinical features of frontotemporal lobar degeneration.

Background/aims: Recent studies suggested a role for pro-inflammatory mediators in frontotemporal lobar degeneration (FTLD). The objective of this study was to evaluate the association of functionally active polymorphisms in pro-inflammatory cytokine genes with the occurrence and the clinical features of the disease.

Methods: Using a case-control study, we compared allelic and genotypic frequencies of several polymorphisms in the interleukin (IL)-1alpha, interleukin (IL)-1beta, interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha genes between 110 FTLD patients and 119 healthy controls.

Haplotype analysis confirms the association between the HCRTR2 gene and cluster headache.

Background: Several studies suggested that genetic factors play a role in cluster headache (CH) susceptibility. We found a significant association between the 1246 G>A polymorphism of the hypocretin receptor-2 (HCRTR2) gene and the disease. This association was confirmed in a large study from Germany but was not replicated in a dataset of CH patients from Northern Europe.

Tumor necrosis factor-alpha gene and cerebral aneurysms.

Objective: The pathogenesis of intracranial aneurysms is still uncertain. In addition to atherosclerosis, immunological factors may play a role in the disease. Recent studies have suggested that tumor necrosis factor-alpha (TNF-alpha), one of the main proinflammatory cytokines, may play a key role in the formation and rupture of cerebral aneurysms.