Time filter

Source Type

Port Adelaide, Australia

Tijero B.,Service of Neurology | Tijero B.,University of the Basque Country | Gomez-Esteban J.C.,Service of Neurology | Gomez-Esteban J.C.,University of the Basque Country | And 9 more authors.
Clinical Autonomic Research | Year: 2010

Introduction Here we report the case of an asymptomatic carrier of the E46K substitution in a-synuclein gene where we have documented that cardiac sympathetic denervation precedes nigrostriatal dopaminergic loss. Material and methods She has been followed up regularly with standard neurological examination, UPDRS, neuropsychological formal testing, parkinson disease sleep scale-PDSS, Epworth scale, Hamilton-D scale, SCOPA Aut, orthostatic hypotension test, brief smell identification test, polysomnography, cerebral 123-I-FP-CIT SPECT, and, 123I-MIBG cardiac scintigraphy. Results She shows no presence of orthostatic hypotension. Olfactory test results demonstrate normal limits. In the PSG the nocturnal sleep shows mild abnormalities although the sleep efficiency and stage proportion remain under normal limits. The 123-I-FP-CIT SPECT is normal; in contrast, the 123I-MIBG cardiac scintigraphy shows a complete lack of isotopic uptake compatible with a severe sympathetic myocardial denervation. Conclusion This example of monogenic autosomal dominant parkinsonism due to an a-synuclein mutation favours the hypothesis that peripheral autonomous nervous system involvement occurs earlier than the CNS degeneration. © Springer-Verlag 2010. Source

Kauffman M.A.,University of Buenos Aires | Kauffman M.A.,Neurogenetics Laboratory | Gonzalez-Moron D.,University of Buenos Aires | Garcea O.,Neuroimmunology Unit | Villa A.M.,Neuroimmunology Unit
Molecular Biology Reports | Year: 2012

Systemic autoinflammatory diseases are genetic disorders characterized by seemingly unprovoked inflammation, without major involvement of the adaptive immune system. Among them it is recognized the TNF receptor associated periodic syndrome (TRAPS) caused by mutations in the TNFRSF1A gene and characterized by symptoms such as recurrent high fevers, rash, abdominal pain, arthralgia and myalgia. Recent studies have recognized the potential role of TNFRSF1A mutations in Multiple Sclerosis (MS). Our aim was to investigate the role of TNFRSF1A R92Q gene mutation in a cohort of 90 Argentinean MS patients, where we determined the frequency of the TNFRSF1A R92Q mutation. We also compared autoinflammatory symptoms, MS clinical characteristics and treatment response and tolerability in R92Q carriers and non-carriers. Also, we used a case-control study design to obtain the genotypes of 78 healthy controls and assess the role of this mutation as a risk factor for MS. We found that five patients (5.5%) carried the R92Q mutation, four reported autoinflammatory symptoms previous to MS onset. We found no differences in MS clinical features, treatment response and tolerability between carriers and non-carriers. R92Q mutation was more frequent in MS patients as compared to controls. This increases the risk to develop MS in about 4.5 times. The TNFRSF1A R92Q mutation is a common finding in Argentinean MS patients. This genetic variant might be a risk factor for MS. © 2011 Springer Science+Business Media B.V. Source

Pablo L.E.,University of Zaragoza | Pablo L.E.,Aragones Institute of Health science | Garcia-Martin E.,University of Zaragoza | Garcia-Martin E.,Aragones Institute of Health science | And 9 more authors.
Molecular Vision | Year: 2011

Purpose: To present full ophthalmologic examination and retinal nerve fiber layer (RNFL) photographs of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) patients showing significant increases in RNFL thickness compared to healthy subjects, but without myelinated retinal fibers. Methods: The study design was observational case series. Ten eyes of five patients with molecular confirmation of ARSACS underwent a full ophthalmologic examination that included clinical history, visual acuity, biomicroscopy of the anterior segment, gonioscopy, Goldmann applanation tonometry, central corneal ultrasonic pachymetry, ophthalmoscopy of the posterior segment, standard automatic perimetry (Humphrey field), simultaneous stereophotographs of the optic disc after mydriasis, a series of five red-free digital fundus photographs for RNFL evaluation, topographic analysis of the optic disc using the Heidelberg retina tomography, and measurement of peripapillary RNFL thickness with Cirrus optical coherence tomography. Results: All patients showed abnormal visual fields, normal optic discs with a mild to strikingly increased visibility of RNFL in color stereophotographs, normal Heidelberg tomography, and moderate to markedly increased RNFL thickness in Cirrus tomography (average thickness ranging from 119 μm to 220 μm). Conclusions: We found evidence of RNFL hypertrophy in ARSACS patients that may have been interpreted as hypermyelinated retinal fibers in previous reports. A revision of ARSACS diagnostic criteria, particularly with regard to retinal alterations, is necessary. © 2011 Molecular Vision. Source

Fullston T.,Neurogenetics Laboratory | Fullston T.,University of Adelaide | Brueton L.,Clinical Genetics Unit | Willis T.,Birmingham Childrens Hospital | And 6 more authors.
European Journal of Human Genetics | Year: 2010

Aristaless-related homeobox (ARX) gene mutations cause a diverse spectrum of disorders of the human brain, including lissencephaly, various forms of epilepsy and non-syndromic mental retardation. We have identified a novel mutation, c.81CG (p.Y27X), within the ARX gene in a family with two affected male cousins. One of the boys was diagnosed with an early infantile epileptic encephalopathy also known as Ohtahara syndrome, whereas his cousin had been diagnosed with West syndrome (WS). Both patients have normal genitalia and neither have lissencephaly. The ARX mutation identified is predicted to yield a severely truncated protein of only 26 amino acids and can be considered as a null mutation. Somewhat surprisingly, however, it does not yield the X-linked lissencephaly with ambiguous genitalia (XLAG) syndrome. We proposed that the ARX mRNA translation re-initiated at the next AUG codon at position c.121-123 (aa 41) and, thus, partly rescued these patients from XLAG. Our in vitro studies show that this N-terminally truncated ARX protein (p.M41-C562) is detected by western immunoblot in lysates from cells transiently transfected with an ARX over-expression construct containing the c.81CG mutation. Although these findings widen the spectrum of clinical phenotypes because of mutations in the ARX gene, they also emphasize the molecular pathogenetic effect of individual mutations as well as the effect of genetic background resulting in intrafamilial clinical heterogeneity for these mutations. © 2010 Macmillan Publishers Limited All rights reserved. Source

Russo M.,University College London | Russo M.,Messina University | Laura M.,University College London | Polke J.M.,Neurogenetics Laboratory | And 9 more authors.
Neuromuscular Disorders | Year: 2011

Charcot-Marie-Tooth disease (CMT) is the commonest hereditary neuropathy encompassing a large group of clinically and genetically heterogeneous disorders. The commonest form of CMT, CMT1A, is usually caused by a 1.4 megabase duplication of chromosome 17 containing the PMP22 gene. Mutations of PMP22 are a less common cause of CMT. We describe clinical, electrophysiological and molecular findings of 10 patients carrying PMP22 missense mutations. The phenotype varied from mild hereditary neuropathy with liability to pressure palsies (HNPP) to severe CMT1. We identified six different point mutations, including two novel mutations. Three families were also found to harbour a Thr118Met mutation. Although PMP22 point mutations are not common, our findings highlight the importance of sequencing the PMP22 gene in patients with variable CMT phenotypes and also confirm that the PMP22 Thr118Met mutation is associated with a neuropathy albeit with reduced penetrance. © 2010. Source

Discover hidden collaborations