Periquet Magali, Latouche Morwena, Lohmann Ebba, Rawal Nina, De Michele Giuseppe, Ricard Sylvain, Teive Hélio, Fraix Valérie, Vidailhet Marie, Nicholl David, Barone Paolo, Wood Nick W, Raskin Salmo, Deleuze Jean-François, Agid Yves, Dürr Alexandra, Brice Alexis
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Brain. 2003 Jun;126(Pt 6):1271-8. doi: 10.1093/brain/awg136.
Parkin gene mutations are reported to be a major cause of early-onset parkinsonism (age at onset < or = 45 years) in families with autosomal recessive inheritance and in isolated juvenile-onset parkinsonism (age at onset <20 years). However, the precise frequency of parkin mutations in isolated cases is not known. In order to evaluate the frequency of parkin mutations in patients with isolated early-onset parkinsonism according to their age at onset, we studied 146 patients of various geographical origin with an age at onset < or = 45 years. All were screened for mutations in the parkin gene using semi-quantitative polymerase chain reaction combined with sequencing of the entire coding region. We identified parkin mutations in 20 patients including three new exon rearrangements and two new missense mutations. These results, taken in conjunction with those of our previous study (Lücking et al., 2000) show that parkin mutations account for at least 15% (38 out of 246) of our early-onset cases without family history, but that the proportion decreases significantly with increasing age at onset. There were no clinical group differences between parkin cases and other patients with early-onset parkinsonism. However, a single case presenting with cerebellar ataxia several years before typical parkinsonism extends the spectrum of parkin related-disease.
据报道，在常染色体隐性遗传家族性早发性帕金森病（发病年龄≤45岁）及散发性青少年帕金森病（发病年龄<20岁）中，帕金基因突变是主要病因。然而，散发病例中帕金基因突变的确切频率尚不清楚。为了根据发病年龄评估散发性早发性帕金森病患者中帕金基因突变的频率，我们研究了146名来自不同地区、发病年龄≤45岁的患者。所有患者均采用半定量聚合酶链反应结合整个编码区测序的方法筛查帕金基因突变。我们在20名患者中发现了帕金基因突变，其中包括3种新的外显子重排和2种新的错义突变。这些结果与我们之前的研究结果（Lücking等人，2000年）共同表明，在我们无家族史的早发性病例中，帕金基因突变至少占15%（246例中有38例），但该比例随发病年龄的增加而显著降低。帕金基因突变病例与其他早发性帕金森病患者之间在临床分组上没有差异。然而，有1例患者在出现典型帕金森病症状数年前出现小脑共济失调，这扩展了帕金基因相关疾病的范围。
