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ABSTRACT: Huntington's disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington's disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and chorea-acanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype.
Arquivos de neuro-psiquiatria 06/2011; 69(3):419-23. · 0.55 Impact Factor
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Stéphanie Millecamps,
François Salachas,
Cécile Cazeneuve,
Paul Gordon,
Bernard Bricka,
Agnès Camuzat,
Léna Guillot-Noël, Odile Russaouen,
Gaëlle Bruneteau,
Pierre-François Pradat, [......],
Philippe Couratier,
Didier Hannequin,
Danielle Seilhean,
Isabelle Le Ber,
Philippe Corcia,
William Camu,
Alexis Brice,
Guy Rouleau,
Eric LeGuern,
Vincent Meininger
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ABSTRACT: Mutations in SOD1, ANG, VAPB, TARDBP and FUS genes have been identified in amyotrophic lateral sclerosis (ALS).
The relative contributions of the different mutations to ALS were estimated by systematically screening a cohort of 162 families enrolled in France and 500 controls (1000 chromosomes) using molecular analysis techniques and performing phenotype-genotype correlations.
31 pathogenic missense mutations were found in 36 patients (20 SOD1, 1 ANG, 1 VAPB, 7 TARDBP and 7 FUS). Surprisingly two FUS mutation carriers also harboured ANG variants. One family of Japanese origin with the P56S VAPB mutation was identified. Seven novel mutations (three in SOD1, two in TARDBP, two in FUS) were found. None of them was detected in controls. Segregation of detected mutations with the disease was confirmed in 11 families including five pedigrees carrying the novel mutations. Clinical comparison of SOD1, TARDBP, FUS and other familial ALS patients (with no mutation in the screened genes) revealed differences in site of onset (predominantly lower limbs for SOD1 and upper limbs for TARDBP mutations), age of onset (younger with FUS mutations), and in lifespan (shorter for FUS carriers). One third of SOD1 patients survived more than 7 years: these patients had earlier disease onset than those presenting with a more typical course. Differences were also observed among FUS mutations, with the R521H FUS mutation being associated with longer disease duration.
This study identifies new genetic associations with ALS and provides phenotype-genotype correlations with both previously reported and novel mutations.
Journal of Medical Genetics 08/2010; 47(8):554-60. · 6.36 Impact Factor
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ABSTRACT: A K17I mutation in the ANG gene encoding angiogenin has been identified in a case that we previously published as ALS with neuronal intranuclear protein inclusions (Seilhean et al. in Acta Neuropathol 108:81-87, 2004). These inclusions were immunoreactive for smooth muscle alpha-actin but not for angiogenin. Moreover, they were not labeled by anti-TDP-43 antibodies, while numerous cytoplasmic inclusions immunoreactive for ubiquitin, p62 and TDP-43 were detected in both oligodendrocytes and neurons in various regions of the central nervous system. In addition, expression of smooth muscle alpha-actin was increased in the liver where severe steatosis was observed. This is the first neuropathological description of a case with an ANG mutation. Angiogenin is known to interact with actin. Like other proteins involved in ALS pathogenesis, such as senataxin, TDP-43 and FUS/TLS, it plays a role in RNA maturation.
Acta Neuropathologica 06/2009; 118(4):561-73. · 9.32 Impact Factor
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Guilherme G. Riccioppo Rodrigues MD,
Ruth H. Walker MB, ChB, PhD,
Alexis Brice MD,
Cécile Cazeneuve PhD,
Odile Russaouen BSc,
PhD Helio A.G. Teive MD,
Renato Puppi Munhoz MD,
Nilson Becker MD,
PhD Salmo Raskin MD,
PhD Lineu Cesar Werneck MD, [......],
Alexis Brice,
Cécile Cazeneuve, Odile Russaouen,
Helio A.G. Teive,
Renato Puppi Munhoz,
Nilson Becker,
Salmo Raskin,
Lineu Cesar Werneck,
Wilson Marques Junior,
Vitor Tumas
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ABSTRACT: Huntington's disease-like 2 (HDL2) is a neurodegenerative disorder found in people of African ancestry with clinical, radiological, and neuropathological manifestations similar to Huntington's disease (HD). HDL2 is caused by a pathological expansion of CAG/CTG triplets in exon 2A of the JPH3 gene. We describe four cases of HDL2 from four unrelated families, and discuss their clinical findings. HDL2 should be considered in every patient with an HD-like phenotype who tests negative for the HD mutation, even if African ancestry is not immediately apparent. © 2008 Movement Disorder Society
Movement Disorders 11/2008; 23(15):2244 - 2247. · 4.51 Impact Factor
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Guilherme G Riccioppo Rodrigues,
Ruth H Walker,
Alexis Brice,
Cécile Cazeneuve, Odile Russaouen,
Helio A G Teive,
Renato Puppi Munhoz,
Nilson Becker,
Salmo Raskin,
Lineu Cesar Werneck,
Wilson Marques Junior,
Vitor Tumas
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ABSTRACT: Huntington's disease-like 2 (HDL2) is a neurodegenerative disorder found in people of African ancestry with clinical, radiological, and neuropathological manifestations similar to Huntington's disease (HD). HDL2 is caused by a pathological expansion of CAG/CTG triplets in exon 2A of the JPH3 gene. We describe four cases of HDL2 from four unrelated families, and discuss their clinical findings. HDL2 should be considered in every patient with an HD-like phenotype who tests negative for the HD mutation, even if African ancestry is not immediately apparent.
Movement Disorders 10/2008; 23(15):2244-7. · 4.51 Impact Factor
