Massimo Pandolfo

..These mice were viable and did not develop anomalies of motor coordination, iron metabolism or response to iron loading. Repeats were meiotically and mitotically stable...

..Hemicerebellectomy blocked the enhancement of the corticomotor response. The cerebellum is a key player in this form of short-term plasticity...

....

..At the same time, the complex pathogenesis of Friedreich ataxia started to be unraveled. Herein, I review our current knowledge of the disease and how it is contributing to the development of therapeutic approaches...

..Epilepsy due to inherited metabolic diseases, chromosomal abnormalities, phakomatoses, or malformations of cortical development is reviewed elsewhere...

....

..There have been recent advances in discovering such factors, in particular those underlying risk to medication toxicity...

..In addition to a review of the clinicopathological features of FRDA, a discussion of recent advances in our understanding of the underlying molecular mechanisms is provided...

..To understand FRDA pathogenesis and to design novel therapeutic strategies, we must first precisely identify the cellular role of frataxin...

..This condition seems to respond to idebenone, a coenzyme Q analog that has antioxidant and oxidative-phosphorylation-stimulating properties...

..Neurogenetics is a recent addition to the areas of the interest of the department; research in neurogenetics includes basic investigations as well as clinical studies and focuses on inherited ataxias and genetic epilepsies...

..Regulatory mechanisms in the cytosol would then sense a post-mitochondrial iron pool. Much circumstantial evidence from genetically manipulated yeast and from human diseases supports this model...

....

....

..In contrast, the promoter variants were significant predictors of IS, suggesting that quantitative rather than qualitative variation of apoE is related to IS...

..The risk variant on chromosome 9, tagged by rs10757278, is associated with coronary heart disease in the Belgian population, but not with isolated CVD. These findings suggest different pathogenic mechanisms in CAD versus CVD...

....

..The hypothesis of AMPA neurotoxicity, which has convincing arguments during chronic exposure, is challenged in this model of acute cerebellar nuclear toxicity of alcohol...

....

..This case illustrates the fact that contrast echocardiography may fail to identify intrapulmonary shunts when a resting patent foramen ovale coexists...

....

..After one month of steroid treatment, the patient was walking alone. This case raises the question whether IVIG is to be considered as first line treatment for diabetes associated CIDP...

..2 was 72%,with a specificity of 69.4%. We conclude that, when used as originally proposed, ACE is very accurate for the detection of dementia, but much less effective in discriminating the most common frontal variant of FTD...

..We hypothesized that subclinical left ventricular (LV) dysfunction may occur in 'FRDA patients who have normal LV ejection fraction (LVEF) and mass...

..FRDA patients have a high prevalence of diabetes, the pathogenesis of which is not known. We aimed to evaluate the relative contribution of insulin resistance and β-cell failure and the pathogenic mechanisms involved in FRDA diabetes...

..However, the pathogenic role of GAD-Ab in neurological diseases remains a matter of debate...

..We postulate that a similar neuroprotective effect of NPCs may be applicable to other cerebellar degenerative diseases...

..Sequence analysis of the five coding exons of the frataxin gene should be performed in clinically affected individuals who are heterozygous for an expanded GAA repeat to identify point mutations...

..We studied whether the PCSK9 gene is linked to the risk of ischemic stroke (IS) and with the development of intracranial atherosclerosis...

..These results demonstrate that inhibition of SREBPs decreases cholesterol synthesis in HepG2 cells both in the absence and presence of homocysteine. SKI-1/S1P inhibition may cause widespread changes in other key metabolic pathways...

..Based on the present results and earlier published data, anti-inflammatory and antiapoptotic treatment could be beneficial in NPC...

..Therapeutic attempts are already using anti-oxidant strategies and such efforts are likely to be enhanced by the rapid availability of animal models of the disease...

..Here, the authors describe a patient with bilateral anterior ponto-cerebellar ischemic lesions associated with major neuropsychological deficits. Cerebral PET and SPECT demonstrated no metabolic defect in supratentorial areas...

..The long normal alleles more frequently showed the 17A haplotype. Our data seem to suggest that all the E alleles come from LN alleles, while LN alleles come from a defined subclass of SN alleles...

..Several hypotheses for frataxin function were evaluated in tgFxn mice. In particular, we observed that TgFxn mice show an altered response during hematopoietic differentiation, suggesting that frataxin may directly affect heme synthesis...

..In addition, these results suggest that frataxin mutations may have a modifier role in HH, that predisposes to cardiomyopathy...

..The identification of a core set of genes changing early in the FRDA pathogenesis can be a useful tool in both clarifying the disease process and in evaluating new therapeutic strategies...

..The Epilepsy Genetics (EPIGEN) Consortium was established to undertake genetic mapping analyses with augmented statistical power to detect variants that influence the development and treatment of common forms of epilepsy...

..The patient also responded clinically to carnitine supplementation, suggesting a potential palliative therapy for the disease...

..Factors such as somatic mosaicism, repeat interruptions, modifying mutations and environmental factors must also be considered...

..Although some of the factors have been defined as genetic modifier factors in previous studies, none of the genes encoding GRIK2, TBP, BDNF and ZDHHC17 could be identified as a genetic modifier for HD...

..In this group, the allelic variation on locus S18Y is responsible for 1.1% of the variance in the HD age-at-onset, and the rare Y allele is associated with younger-aged cases...

..Altered adenosine transport across the membrane of HPRT-deficient lymphocytes has been reported, suggesting adenosine involvement in LND...

..Therefore, this study identifies novel molecular targets that are regulated by Atxn1 which might contribute to the motor deficits in SCA1, and provides new insights into the mechanisms by which Atxn1 co-regulates transcription...

....

..A gene for FPEVF was mapped to chromosome 22q12 in two distantly related French-Canadian families...

..The locus on chromosome 12 does not contain genes for any other form of PME, nor does it have genes known to be related to cystatin B. This represents a new form of PME and we have designated the locus as EPM1B...

..These findings have implications for the large number of patients with limited clinical features of TSC and for genetic counseling in these families...

..We hope that the real-time PCR approach will provide a useful and reliable method to diagnose LNS carriers of large deletions in HPRT gene...

..Stress response pathways will be important areas for elucidation of episodic disease genetics where stress is a common precipitant of many common disorders like epilepsy, migraine and cardiac arrhythmias...