Microdeletions detected using chromosome microarray in children with suspected genetic movement disorders: a single-centre study
Microdeletions detected using chromosome microarray in children with suspected genetic movement disorders: a single-centre study
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DOI：
10.1111/j.1469-8749.2012.04287.x
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发表时间：
2012-07-01
影响因子：
3.8
通讯作者：
Peters, Greg B.
中科院分区：
文献类型：
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作者：
Dale, Russell C.;Grattan-Smith, Padraic;Peters, Greg B.
目的 染色体微阵列 (CMA) 可以确定拷贝数变异，例如微缺失或微重复。肌阵挛肌张力障碍和良性遗传性舞蹈病患者中分别描述了运动障碍基因的微缺失，包括ε肌聚糖（SGCE）和甲状腺转录因子1（TITF1）。我们研究了 CMA 是否是调查疑似遗传性运动障碍儿童的一个有价值的工具。方法 如果存在阳性一级家族史，或以下两个或多个因素，则怀疑患有遗传性运动障碍：磁共振成像正常或接近正常、脑损伤史阴性、代谢紊乱检查阴性。排除抽动障碍。前瞻性招募了 25 名患者（18 名男性，7 名女性），运动障碍发病的平均年龄为 4 岁零 5 个月（范围 1 个月 14 岁），患有以下原发性运动障碍：肌张力障碍（n = 10）、阵发性运动源性运动障碍（n = 5）、震颤（n = 4）、舞蹈症（n = 3）、肌阵挛（n = 2）和阵发性运动障碍。非运动源性运动障碍 (n=1)。合并症相关特征很常见，特别是发育迟缓或智力障碍（25 例中有 19 例）和注意力缺陷多动障碍（25 例中有 6 例）。使用 Agilent aCGH 60K 阵列进行 CMA。结果 25 名患者中有 7 名存在 CMA 确定的微缺失。没有一个微缺失被认为是良性变异。 4 名患者存在已知运动障碍基因的缺失，包括阵发性运动诱发性运动障碍 (PRRT2；n=2)、SGCE（肌阵挛性肌张力障碍，n=1）和 TITF1（良性遗传性舞蹈病，n=1）。三名患者具有未知但具有潜在意义的新微缺失，包括 14q13.3（舞蹈症，n=1）、19p13.12（震颤，n=1）和 19q13.12（进行性肌张力障碍）。所有七名患者都有相关的神经发育或行为问题。对于疑似遗传运动障碍的患者，尤其是与智力障碍或发育障碍相关的患者，确定拷贝数变异的解释分析可能是有价值的一级研究。微缺失综合征可能有助于寻找新的运动障碍基因。
Aim Chromosome microarray (CMA) can determine copy number variants such as microdeletions or microduplications. Microdeletions of movement disorder genes including epsilon-sarcoglycan (SGCE) and thyroid transcription factor-1 (TITF1) have been described in patients with myoclonus dystonia and benign hereditary chorea respectively. We examined whether CMA is a valuable tool in the investigation of children with suspected genetic movement disorders. Method A genetic movement disorder was suspected if there was a positive first-degree family history, or two or more of the following factors: normal or near-normal magnetic resonance imaging, negative history of brain injury, and negative investigations for metabolic disorders. Tic disorders were excluded. Twenty-five patients (18 males, seven females) with a mean age at movement disorder onset of 4 years 5 month (range 1mo14y) were prospectively recruited with the following primary movement disorders: dystonia (n=10), paroxysmal kinesigenic dyskinesia (n=5), tremor (n=4), chorea (n=3), myoclonus (n=2), and paroxysmal non-kinesigenic dyskinesia (n=1). Comorbid associated features were common, particularly developmental delay or intellectual disability (19 out of 25) and attention-deficithyperactivity disorder (six out of 25). CMA was performed using Agilent aCGH 60K array. Results Seven out of twenty-five patients had a microdeletion determined by CMA. None of the microdeletions were considered benign variants. Four patients had a deletion of a known movement disorder gene including paroxysmal kinesigenic dyskinesia (PRRT2; n=2), SGCE (myoclonus dystonia, n=1), and TITF1 (benign hereditary chorea, n=1). Three patients had novel microdeletions of unknown but potential significance including 14q13.3 (chorea, n=1), 19p13.12 (tremor, n=1), and 19q13.12 (progressive dystonia). All seven patients had associated neurodevelopmental or behavioural problems. Interpretation Assays that determine copy number variants may be a valuable first-tier investigation in patients with suspected genetic movement disorders, particularly when associated with intellectual disability or developmental disorders. Microdeletion syndromes may help the search for new movement disorder genes.