SCA15 Due to Large ITPR1 Deletions in a Cohort of 333 White Families With Dominant Ataxia
SCA15 Due to Large ITPR1 Deletions in a Cohort of 333 White Families With Dominant Ataxia
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DOI：
10.1001/archneurol.2011.81
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发表时间：
2011-05-01
影响因子：
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通讯作者：
Brice, Alexis
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文献类型：
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作者：
Marelli, Cecilia;van de Leemput, Joyce;Brice, Alexis
背景资料：目的：研究脊髓小脑性共济失调15型（SCA 15）患者ITPR 1基因缺失的频率和表型。设计：Taqman聚合酶链反应（258例索引病例）或单核苷酸多态性全基因组基因分型（75例索引病例）。（巴黎，法国）和国家衰老研究所分子遗传学单位（Bethesda，马里兰州）。患者：333个常染色体显性小脑共济失调家族的索引病例，编码外显子CAG重复扩增阴性。主要结果测量：ITPR 1拷贝数改变的检测。结果：在333个家系中有6个（1.8%）发现ITPR 1缺失，对应于13例SCA 15患者。发病时年龄范围为18 - 66岁（平均[SD]年龄，35 [16]岁）。除1例患者出现孤立性上肢震颤外，其余患者均表现为小脑性步态共济失调。虽然家庭进行了测试，无论他们的表型，SCA 15患者有一个同质的表型，其特点是缓慢进行性小脑共济失调。然而，偶尔存在锥体束征（2例患者）和轻度认知问题（2例患者）。放射学检查结果显示，全球或占主导地位的蠕虫小脑萎缩在所有patients.Conclusions：在这个系列中，ITPR 1缺失是罕见的，约占1%的所有常染色体显性遗传性小脑共济失调。SCA 15表型主要包括一个缓慢进行性孤立的小脑共济失调，发病年龄不同;可能存在额外的锥体细胞综合征和执行功能问题。
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 Epiniere of the Salpetriere 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.