Information de reference pour ce titreAccession Number: | 00005068-201101000-00010.
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Author: | Brahim, H'mida-Ben D. 1,2,3; M'zahem, A. 4; Assoum, M. 1,2; Bouhlal, Y. 5; Fattori, F. 6; Anheim, M. 1,2,7; Ali-Pacha, L. 8; Ferrat, F. 9; Chaouch, M. 9; Lagier-Tourenne, C. 1,2; Drouot, N. 1,2; Thibaut, C. 1,2; Benhassine, T. 10; Sifi, Y. 4; Stoppa-Lyonnet, D. 11,12; N'Guyen, K. 13; Poujet, J. 13; Hamri, A. 4; Hentati, F. 5; Amouri, R. 5; Santorelli, F. M. 6; Tazir, M. 8; Koenig, M. 1,2
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Institution: | (1)Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/Universite de Strasbourg 67404 Illkirch, France (2)Hopitaux Universitaires de Strasbourg 67000 Strasbourg, France (3)Laboratoire de Cytogenetique, Genetique Moleculaire et Biologie de la Reproduction Humaines, CHU Farhat HACHED 4011 Sousse, Tunisia (4)Centre Hospitalo-Universitaire Ben Badis, Constantine, Algeria (5)Institut de Neurologie, Tunis, Tunisia (6)Molecular Medicine and Neurosciences IRCCS Bambino Gesu Hospital, Rome, Italy (7)Service de Neurologie, Hopitaux Universitaires de Strasbourg 67091 Strasbourg, France (8)Service de Neurologie, Centre Hospitalo-Universitaire Mustapha, Alger, Algeria (9)Service de Neurologie, Etablissement Hospitalier Specialise de Ben Aknoun, Alger, Algeria (10)Institut Pasteur, Alger, Algeria (11)Institut Curie, Service de Genetique, INSERM U830 75248 Paris, France (12)Universite Paris Descartes 75270 Paris, France (13)Hopitaux Universitaires de Marseille, Marseille, France
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Title: | Molecular diagnosis of known recessive ataxias by homozygosity mapping with SNP arrays.[Article]
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Source: | Journal of Neurology. 258(1):56-67, January 2011.
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Abstract: | The diagnosis of rare inherited diseases is becoming more and more complex as an increasing number of clinical conditions appear to be genetically heterogeneous. Multigenic inheritance also applies to the autosomal recessive progressive cerebellar ataxias (ARCAs), for which 14 genes have been identified and more are expected to be discovered. We used homozygosity mapping as a guide for identification of the defective locus in patients with ARCA born from consanguineous parents. Patients from 97 families were analyzed with GeneChip Mapping 10K or 50K SNP Affymetrix microarrays. We identified six families homozygous for regions containing the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) gene, two families homozygous for the ataxia-telangiectasia gene (ATM), two families homozygous for the ataxia with oculomotor apraxia type 1 (AOA1) gene, and one family homozygous for the AOA type 2 (AOA2) gene. Upon direct gene testing, we were able to identify a disease-related mutation in all families but one of the two kindred homozygous at the ATM locus. Although linkage analyses pointed to a single locus on chromosome 11q22.1-q23.1 for this family, clinical features, normal levels of serum alpha-foetoprotein as well as absence of mutations in the ATM gene rather suggest the existence of an additional ARCA-related gene in that interval. While the use of homozygosity mapping was very effective at pointing to the correct gene, it also suggests that the majority of patients harbor mutations either in the genes of the rare forms of ARCA or in genes yet to be identified.
(C) 2011 Springer. Part of Springer Science Business Media
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Author Keywords: | Recessive ataxia; Homozygosity mapping; SNP microarrays.
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Language: | English.
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Document Type: | Original Communication: PDF Only.
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Journal Subset: | Clinical Medicine.
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ISSN: | 0340-5354
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NLM Journal Code: | jb7, 0423161
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DOI Number: | https://dx.doi.org/10.1007/s0041...- ouverture dans une nouvelle fenêtre
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