SCA15 due to large ITPR1 deletions in a cohort of 333 white families with dominant ataxia.

Cecilia Marelli, Joyce van de Leemput, Janel O. Johnson, Francois Tison, Christel Thauvin-Robinet, Fabienne Picard, Christine Tranchant, Dena G. Hernandez, Bernard Huttin, Jacques Boulliat, Iban Sangla, Christian Marescaux, Serge Brique, Hélène Dollfus, Sampath Arepalli, Isabelle Benatru, Elisabeth Ollagnon, Sylvie Forlani, John Hardy, Giovanni Stevanin, Alexandra Dürr, Andrew Singleton, Alexis Brice
Arch Neurol. 2011-05-01; 68(5):
DOI: 10.1001/archneurol.2011.81

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1. Arch Neurol. 2011 May;68(5):637-43. doi: 10.1001/archneurol.2011.81.

SCA15 due to large ITPR1 deletions in a cohort of 333 white families with
dominant ataxia.

Marelli C(1), van de Leemput J, Johnson JO, Tison F, Thauvin-Robinet C, Picard F,
Tranchant C, Hernandez DG, Huttin B, Boulliat J, Sangla I, Marescaux C, Brique S,
Dollfus H, Arepalli S, Benatru I, Ollagnon E, Forlani S, Hardy J, Stevanin G,
Dürr A, Singleton A, Brice A.

Author information:
(1)INSERM U975, Centre de Recherche de l’Institut du Cerveau et de la Moelle
Épinière, Groupe Hospitalier Pitié Salpêtrière, 47 Boulevard de l’Hôpital, Paris
Cedex 13, France.

BACKGROUND: Deletions in ITPR1, coding for the inositol-triphosphate receptor
type 1, have been recently identified in spinocerebellar ataxia type 15 (SCA15).
OBJECTIVE: To determine the frequency and the phenotypical spectrum of SCA15.
DESIGN: Taqman polymerase chain reaction (258 index cases) or single-nucleotide
polymorphism genome-wide genotyping (75 index cases).
SETTING: A collaboration between the Centre de Recherche de l’Institut de Cerveau
et de la Moelle Epinière of the Salpêtrière Hospital (Paris, France) and the
Molecular Genetics Unit of the National Institute of Aging (Bethesda, Maryland).
Patients  Index cases of 333 families with autosomal dominant cerebellar ataxia
negative for CAG repeat expansions in coding exons.
MAIN OUTCOME MEASURES: Detection of ITPR1 copy number alterations.
RESULTS: A deletion of ITPR1 was found in 6 of 333 families (1.8%), corresponding
to 13 patients with SCA15. Age at onset ranged from 18 to 66 years (mean [SD]
age, 35 [16] years). The symptom at onset was cerebellar gait ataxia, except in 1
patient with isolated upper limb tremor. Although families were tested
irrespective of their phenotype, patients with SCA15 had a homogeneous phenotype
and were characterized by a slowly progressive cerebellar ataxia. However,
pyramidal signs (2 patients) and mild cognitive problems (2 patients) were
occasionally present. Radiologic findings showed global or predominant vermian
cerebellar atrophy in all patients.
CONCLUSIONS: In this series, ITPR1 deletions were rare and accounted for
approximately 1% of all autosomal dominant cerebellar ataxias. The SCA15
phenotype mostly consists of a slowly progressive isolated cerebellar ataxia with
variable age at onset; an additional pyramidal syndrome and problems in executive
functions may be present.

DOI: 10.1001/archneurol.2011.81
PMCID: PMC3142680
PMID: 21555639 [Indexed for MEDLINE]

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