New Subtype of Spinocerebellar Ataxia With Altered Vertical Eye Movements Mapping to Chromosome 1p32
Por:
Serrano-Munuera, C, Corral-Juan, M, Stevanin, G, San Nicolas, H, Roig, C, Corral, J, Campos, B, de Jorge, L, Morcillo-Suarez, C, Navarro, A, Forlani, S, Durr, A, Kulisevsky, J, Brice, A, Sanchez, I, Volpini, V, Matilla-Duenas, A
Publicada:
1 jun 2013
Resumen:
Importance: To provide clinical and genetic diagnoses for patients' conditions, it is important to identify and characterize the different subtypes of spinocerebellar ataxia (SCA).
Objective: To clinically and genetically characterize a Spanish kindred with pure SCA presenting with altered vertical eye movements.
Design: Family study of ambulatory patients. Electro-oculographic and genetics studies were performed in 2 referral university centers.
Setting: Primary care institutional center in Spain.
Participants: Thirty-six participants from a large Spanish kindred were clinically examined, and 33 family members were genetically examined. Detailed clinical data were obtained from 9 affected relatives. Two ataxic siblings and 2 asymptomatic family members were examined using an enhanced clinical protocol for a follow-up period of 7 years.
Main Outcomes and Measures: High-density genome-wide single-nucleotide polymorphism arrays, along with microsatellite analysis, and genetic linkage studies were performed. Whole-exome sequencing was used for 2 affected relatives. For most patients, the initial symptoms included falls, dysarthria, or clumsiness followed by a complete cerebellar syndrome. For all 9 affected relatives, we observed altered vertical eye movements, as initial ocular signs for 3 of them and for the 2 asymptomatic family members, all having inherited the risk haplotype. Neuroimaging showed isolated cerebellar atrophy.
Results: Initial genome-wide linkage analysis revealed suggestive linkage to chromosome 1p32. Multipoint analysis and haplotype reconstruction further traced this SCA locus to a 0.66-cM interval flanked by D1S200 and D1S2742 (z(max)=6.539; P < .0001). The causative mutation was unidentified by exome sequencing.
Conclusions and Relevance: We report a new subtype of SCA presenting in patients as slow progressing ataxia with altered vertical eye movements linked to a 11-megabase interval on 1p32. The Human Genome Nomenclature Committee has assigned this subtype of ataxia the designation SCA37.
Filiaciones:
Serrano-Munuera, C:
Hosp St Joan de Deu, Dept Internal Med, Neurol Unit, Martorell, Spain
Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain
Corral-Juan, M:
Hlth Sci Res Inst Germans Trias i Pujol, Dept Neurosci, Basic Translat & Mol Neurogenet Res Unit Neurodeg, Badalona, Spain
Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain
Stevanin, G:
Univ Paris 06, INSERM, U975, Ctr Rech Inst Cerveau & Moelle Epiniere,EPHE, Paris, France
Grp Hosp Pitie Salpetriere, CNRS, Unite Mixte Rech 7225, F-75634 Paris, France
San Nicolas, H:
Inst Invest Biomed Bellvitge, Ctr Diagnost Genet Mol, Lhospitalet De Llobregat, Spain
Roig, C:
Hosp Sta, Dept Neurol, Creu I St Pau, Spain
Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain
Corral, J:
Inst Invest Biomed Bellvitge, Ctr Diagnost Genet Mol, Lhospitalet De Llobregat, Spain
Campos, B:
Inst Invest Biomed Bellvitge, Ctr Diagnost Genet Mol, Lhospitalet De Llobregat, Spain
de Jorge, L:
Inst Invest Biomed Bellvitge, Ctr Diagnost Genet Mol, Lhospitalet De Llobregat, Spain
Morcillo-Suarez, C:
Inst Biol Evolut UPF CSIC, Barcelona, Spain
Univ Pompeu Fabra, Natl Inst Bioinformat, Barcelona, Spain
Navarro, A:
Inst Biol Evolut UPF CSIC, Barcelona, Spain
Univ Pompeu Fabra, Natl Inst Bioinformat, Barcelona, Spain
Catalan Inst Res & Adv Studies, Catalonia, Spain
Forlani, S:
Univ Paris 06, INSERM, U975, Ctr Rech Inst Cerveau & Moelle Epiniere,EPHE, Paris, France
Grp Hosp Pitie Salpetriere, CNRS, Unite Mixte Rech 7225, F-75634 Paris, France
Durr, A:
Univ Paris 06, INSERM, U975, Ctr Rech Inst Cerveau & Moelle Epiniere,EPHE, Paris, France
Grp Hosp Pitie Salpetriere, CNRS, Unite Mixte Rech 7225, F-75634 Paris, France
Kulisevsky, J:
Univ Autonoma Barcelona, St Pauls Hosp IIB St Pau, Dept Neurol, Movement Disorders Unit, E-08193 Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain
Brice, A:
Univ Paris 06, INSERM, U975, Ctr Rech Inst Cerveau & Moelle Epiniere,EPHE, Paris, France
Grp Hosp Pitie Salpetriere, CNRS, Unite Mixte Rech 7225, F-75634 Paris, France
Sanchez, I:
Hlth Sci Res Inst Germans Trias i Pujol, Dept Neurosci, Basic Translat & Mol Neurogenet Res Unit Neurodeg, Badalona, Spain
Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain
Volpini, V:
Inst Invest Biomed Bellvitge, Ctr Diagnost Genet Mol, Lhospitalet De Llobregat, Spain
Matilla-Duenas, A:
Hlth Sci Res Inst Germans Trias i Pujol, Dept Neurosci, Basic Translat & Mol Neurogenet Res Unit Neurodeg, Badalona, Spain
Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain
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