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ABSTRACT: In this study, we report the results of a genetic linkage analysis of a large family with photoparoxysmal response, defined by the presence of a photoparoxysmal response (PPR) on EEG. The participants were genotyped using an 8 cM whole genome wide scan, and both parametric and non-parametric linkage analysis were carried out. The parametric analysis by MLINK did not identify any definite conclusion but a region of interest on chromosome 1 near marker D1S2865; and non-parametric linkage analysis found a locus of interest on chromosome 16, near marker D16S2621. The possible confounding factors for, and pathogenic implication of, and the results are discussed.
Epilepsy research 11/2011; 99(1-2):38-45. · 2.48 Impact Factor
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Janet A Brooks,
Henry Houlden,
Anna Melchers,
Ansha J Islam,
Jinhui Ding,
Abi Li,
Reema Paudel,
Tamas Revesz,
Janice L Holton, Nick Wood,
Andrew Lees,
Andrew B Singleton,
Sonja W Scholz
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ABSTRACT: Multiple system atrophy (MSA) and Parkinson's disease (PD) are progressive neurodegenerative disorders with overlapping clinical, biochemical and genetic features. To test the hypothesis that the PD genes parkin and PINK1 also play a role in the pathogenesis of MSA, we performed a mutational screening study involving 87 pathologically proven MSA cases. In parkin we identified eight sequence variants and four heterozygous deletions and in PINK1 we identified nine variants of which two silent mutations have not been previously reported (p.Gly189Gly and p.Arg337Arg). The frequencies of the observed variants were not significantly different from previously published control data and none of the possibly pathogenic variants were found in a homozygous state. Our results indicate that genetic variants at the parkin and PINK1 loci do not play a critical role in the pathogenesis of MSA.
Neurobiology of aging 03/2011; 32(3):548.e5-7. · 5.94 Impact Factor
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Sonja W Scholz,
Henry Houlden,
Claudia Schulte,
Manu Sharma,
Abi Li,
Daniela Berg,
Anna Melchers,
Reema Paudel,
J Raphael Gibbs,
Javier Simon-Sanchez, [......],
Ramon L Rodriguez,
Michael S Okun,
Werner Poewe,
Gregor K Wenning,
John A Hardy,
Andrew B Singleton,
Francesca Del Sorbo,
Susanne Schneider,
Kailash P Bhatia,
Thomas Gasser
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ABSTRACT: To test whether the synucleinopathies Parkinson's disease and multiple system atrophy (MSA) share a common genetic etiology, we performed a candidate single nucleotide polymorphism (SNP) association study of the 384 most associated SNPs in a genome-wide association study of Parkinson's disease in 413 MSA cases and 3,974 control subjects. The 10 most significant SNPs were then replicated in additional 108 MSA cases and 537 controls. SNPs at the SNCA locus were significantly associated with risk for increased risk for the development of MSA (combined p = 5.5 x 10(-12); odds ratio 6.2) [corrected].
Annals of Neurology 06/2009; 65(5):610-4. · 11.09 Impact Factor
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Andrew West,
Magali Periquet,
Sarah Lincoln,
Christoph B Lücking,
David Nicholl,
Vincenzo Bonifati,
Nina Rawal,
Thomas Gasser,
Ebba Lohmann,
Jean-François Deleuze,
Demetrius Maraganore,
Allan Levey, Nick Wood,
Alexandra Dürr,
John Hardy,
Alexis Brice,
Matt Farrer
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ABSTRACT: Mutations in the Parkin gene cause juvenile and early onset Parkinsonism. While Parkin-related disease is presumed to be an autosomal-recessive disorder, cases have been reported where only a single Parkin allele is mutated and raise the possibility of a dominant effect. In this report, we re-evaluate twenty heterozygous cases and extend the mutation screening to include the promoter and intron/exon boundaries. Novel deletion, point and intronic splice site mutations are described, along with promoter variation. These data, coupled with a complete review of published Parkin mutations, confirms that not only is recessive loss of Parkin a risk factor for juvenile and early onset Parkinsonism but that Parkin haplo-insufficiency may be sufficient for disease in some cases.
American Journal of Medical Genetics 08/2002; 114(5):584-91.
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ABSTRACT: A coding substitution (I93M) in the ubiquitin carboxyterminal L1 (UCH-L1) gene has recently been identified in a German family with Parkinson's disease. We have sequenced the entire coding region of the gene in 11 families who have a pattern of disease consistent with autosomal dominant inheritance. We found a polymorphism (S18Y) in exon 3, two polymorphisms in the 5' non-coding region, upstream of the transcription start, and an insertion/deletion polymorphism in intron 4. The S18Y allele is present on ∼20% of chromosomes in a Caucasian population. These changes are, therefore, unlikely to be pathogenic. We conclude that the I93M variant must either be a rare cause of disease or a harmless substitution whose occurrence in the family reflects a chance co-occurrence.
Neuroreport 02/1999; 10(2):427-429. · 1.66 Impact Factor
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Gilles David,
Nacer Abbas,
Giovanni Stevanin,
Alexandra Dürr,
Gaël Yvert,
Géraldine Cancel,
Chantal Weber,
Georges Imbert,
Frédéric Saudou,
Eric Antoniou,
Harry Drabkin,
Robert Gemmill,
Paola Giunti,
Ali Benomar, Nick Wood,
Merle Ruberg,
Yves Agid,
Jean-Louis Mandel,
Alexis Brice
