New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32.

Carmen Serrano-Munuera, Marc Corral-Juan, Giovanni Stevanin, Hector San Nicolás, Carles Roig, Jordi Corral, Berta Campos, Laura de Jorge, Carlos Morcillo-Suárez, Arcadi Navarro, Sylvie Forlani, Alexandra Durr, Jaime Kulisevsky, Alexis Brice, Ivelisse Sánchez, Victor Volpini, Antoni Matilla-Dueñas
JAMA Neurol. 2013-06-01; 70(6): 764
DOI: 10.1001/jamaneurol.2013.2311

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1. JAMA Neurol. 2013 Jun;70(6):764-71. doi: 10.1001/jamaneurol.2013.2311.

New subtype of spinocerebellar ataxia with altered vertical eye movements mapping
to chromosome 1p32.

Serrano-Munuera C(1), Corral-Juan M, Stevanin G, San Nicolás H, Roig C, Corral J,
Campos B, de Jorge L, Morcillo-Suárez C, Navarro A, Forlani S, Durr A, Kulisevsky
J, Brice A, Sánchez I, Volpini V, Matilla-Dueñas A.

Author information:
(1)Neurology Unit, Department of Internal Medicine, Hospital St Joan de Deu,
Martorell, Spain.

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.

DOI: 10.1001/jamaneurol.2013.2311
PMID: 23700170 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus