| 1 | Parkinsonism Relat. Disord. 2008 Aug 14: 465-70 |
|---|---|
| PMID | 18342564 |
| Title | Autosomal dominant dopa-responsive parkinsonism in a multigenerational Swiss family. |
| Abstract | To describe a large family with autosomal dominant parkinsonism. Seven genes are directly implicated in autosomally inherited parkinsonism. However, there are several multigenerational large families known with no identifiable mutation. Family members were evaluated clinically, by history and chart review. Genetic investigation included SCA2, SCA3, UCHL1, SNCA, LRRK2, PINK1, PRKN, PGRN, FMR1 premutation, and MAPT. The proband underwent brain fluorodopa PET (FD-PET) scan, and one autopsy was available. Eleven patients had a diagnosis of Parkinson's disease (PD), nine women. Mean age of onset was 52 with tremor-predominant dopa-responsive parkinsonism. Disease progression was slow but severe motor fluctuations occurred. One patient required subthalamic nucleus deep-brain stimulation with a good motor outcome. One patient had mental retardation, schizophrenia and became demented, and another patient was demented. Three patients and also two unaffected subjects had mild learning difficulties. All genetic tests yielded negative results. FD-PET showed marked asymmetric striatal tracer uptake deficiency, consistent with PD. Pathological examination demonstrated no Lewy bodies and immunostaining was negative for alpha-synuclein. Apart from a younger age of onset and a female predominance, the phenotype was indistinguishable from sporadic tremor-predominant PD, including FD-PET scan results. As known genetic causes of autosomal dominant PD were excluded, this family harbors a novel genetic defect. |
| SCZ Keywords | schizophrenia |
| 2 | Neurosci. Lett. 2014 Apr 566: 210-5 |
| PMID | 24631561 |
| Title | No association between genetic variants of the LRRK2 gene and schizophrenia in Han Chinese. |
| Abstract | Mitochondrial dysfunction was widely reported in schizophrenia patients in recent studies. Leucine-rich repeat kinase 2 (LRRK2) is a mitochondrial protein, and mutations in the LRRK2 gene can induce mitochondrial dysfunction. LRRK2 mutations have been reported to be the most frequent genetic cause of Parkinson's disease (PD). We were interested in whether LRRK2 variants also play a role in schizophrenia. In this study, we genotyped 12 genetic variants (including 4 tag SNPs and 8 disease-associated variants) in the LRRK2 gene in a total of 2449 samples composed of two independent Han Chinese schizophrenia case-control cohorts (486 schizophrenia patients and 480 healthy controls from Hunan Province; 624 schizophrenia patients and 859 healthy controls from Shanghai). We compared the genotype, allele and haplotype frequencies of those SNPs between cases and controls. Statistical analyses revealed no association between LRRK2 variants/haplotypes and schizophrenia in these two schizophrenia case-control cohorts and the combined samples. Our results indicated that the LRRK2 variants are unlikely to be actively involved in schizophrenia in Han Chinese. |
| SCZ Keywords | schizophrenia |
| 3 | Front Neurosci 2016 -1 10: 150 |
| PMID | 27064956 |
| Title | EFhd2, a Protein Linked to Alzheimer's Disease and Other Neurological Disorders. |
| Abstract | EFhd2 is a conserved calcium binding protein linked to different neurological disorders and types of cancer. Although, EFhd2 is more abundant in neurons, it is also found in other cell types. The physiological function of this novel protein is still unclear, but it has been shown in vitro to play a role in calcium signaling, apoptosis, actin cytoskeleton, and regulation of synapse formation. Recently, EFhd2 was shown to promote cell motility by modulating the activity of Rac1, Cdc42, and RhoA. Although, EFhd2's role in promoting cell invasion and metastasis is of great interest in cancer biology, this review focusses on the evidence that links EFhd2 to Alzheimer's disease (AD) and other neurological disorders. Altered expression of EFhd2 has been documented in AD, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and schizophrenia, indicating that Efhd2 gene expression is regulated in response to neuropathological processes. However, the specific role that EFhd2 plays in the pathophysiology of neurological disorders is still poorly understood. Recent studies demonstrated that EFhd2 has structural characteristics similar to amyloid proteins found in neurological disorders. Moreover, EFhd2 co-aggregates and interacts with known neuropathological proteins, such as tau, C9orf72, and LRRK2. These results suggest that EFhd2 may play an important role in the pathophysiology of neurodegenerative diseases. Therefore, the understanding of EFhd2's role in health and disease could lead to decipher molecular mechanisms that become activated in response to neuronal stress and degeneration. |
| SCZ Keywords | schizophrenia |