title: SCA15 due to large ITPR1 deletions in a cohort of 333 white families with dominant ataxia.
abstract: 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.
  
  
  METHODS
  Taqman polymerase chain reaction (258 index cases) or single-nucleotide polymorphism genome-wide genotyping (75 index cases).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marelli
authors.forename: Joyce
authors.initials: J
authors.lastname: van de Leemput
authors.forename: Janel O
authors.initials: JO
authors.lastname: Johnson
authors.forename: Francois
authors.initials: F
authors.lastname: Tison
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: Fabienne
authors.initials: F
authors.lastname: Picard
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchant
authors.forename: Dena G
authors.initials: DG
authors.lastname: Hernandez
authors.forename: Bernard
authors.initials: B
authors.lastname: Huttin
authors.forename: Jacques
authors.initials: J
authors.lastname: Boulliat
authors.forename: Iban
authors.initials: I
authors.lastname: Sangla
authors.forename: Christian
authors.initials: C
authors.lastname: Marescaux
authors.forename: Serge
authors.initials: S
authors.lastname: Brique
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Sampath
authors.initials: S
authors.lastname: Arepalli
authors.forename: Isabelle
authors.initials: I
authors.lastname: Benatru
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ollagnon
authors.forename: Sylvie
authors.initials: S
authors.lastname: Forlani
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001284:Atrophy; D002531:Cerebellum / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009759:Nystagmus, Pathologic / Q000235:genetics; D010375:Pedigree; D012438:Saccades / Q000235:genetics; D017422:Sequence Analysis, DNA; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology; D044465:White People / Q000235:genetics*
chemical_list: C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors