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.
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.
Authors: Y Miyoshi; T Yamada; M Tanimura; T Taniwaki; K Arakawa; Y Ohyagi; H Furuya; K Yamamoto; K Sakai; T Sasazuki; J Kira Journal: Neurology Date: 2001-07-10 Impact factor: 9.910
Authors: V A Street; M M Bosma; V P Demas; M R Regan; D D Lin; L C Robinson; W S Agnew; B L Tempel Journal: J Neurosci Date: 1997-01-15 Impact factor: 6.167
Authors: K Hara; A Shiga; H Nozaki; J Mitsui; Y Takahashi; H Ishiguro; H Yomono; H Kurisaki; J Goto; T Ikeuchi; S Tsuji; M Nishizawa; O Onodera Journal: Neurology Date: 2008-06-25 Impact factor: 9.910
Authors: Joyce van de Leemput; Jayanth Chandran; Melanie A Knight; Lynne A Holtzclaw; Sonja Scholz; Mark R Cookson; Henry Houlden; Katrina Gwinn-Hardy; Hon-Chung Fung; Xian Lin; Dena Hernandez; Javier Simon-Sanchez; Nick W Wood; Paola Giunti; Ian Rafferty; John Hardy; Elsdon Storey; R J McKinlay Gardner; Susan M Forrest; Elizabeth M C Fisher; James T Russell; Huaibin Cai; Andrew B Singleton Journal: PLoS Genet Date: 2007-05-16 Impact factor: 5.917
Authors: Alexander S Brown; Pratap Meera; Banu Altindag; Ravi Chopra; Emma M Perkins; Sharan Paul; Daniel R Scoles; Eric Tarapore; Jessica Magri; Haoran Huang; Mandy Jackson; Vikram G Shakkottai; Thomas S Otis; Stefan M Pulst; Scott X Atwood; Anthony E Oro Journal: Proc Natl Acad Sci U S A Date: 2018-12-07 Impact factor: 11.205
Authors: Katherine E Hekman; Guo-Yun Yu; Christopher D Brown; Haipeng Zhu; Xiaofei Du; Kristina Gervin; Dag Erik Undlien; April Peterson; Giovanni Stevanin; H Brent Clark; Stefan M Pulst; Thomas D Bird; Kevin P White; Christopher M Gomez Journal: Hum Mol Genet Date: 2012-09-21 Impact factor: 6.150
Authors: Jillian P Casey; Taisei Hirouchi; Chihiro Hisatsune; Bryan Lynch; Raymond Murphy; Aimee M Dunne; Akitoshi Miyamoto; Sean Ennis; Nick van der Spek; Bronagh O'Hici; Katsuhiko Mikoshiba; Sally Ann Lynch Journal: J Neurol Date: 2017-06-15 Impact factor: 4.849
Authors: Philip W Tipton; Kimberly Guthrie; Audrey Strongosky; Ronald Reimer; Zbigniew K Wszolek Journal: Neurol Neurochir Pol Date: 2016-11-10 Impact factor: 1.621