Genetics of Parkinson's disease: the yield.
Genetics of Parkinson's disease: the yield.
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DOI：
10.1016/s1353-8020(13)70011-7
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发表时间：
2014-01-01
影响因子：
4.1
通讯作者：
Wider, Christian
中科院分区：
文献类型：
--
作者：
Spatola, Marianna;Wider, Christian
与家族性帕金森病（PD）有关的基因的发现为导致神经变性的分子事件提供了新的见解。临床上，遗传决定性PD患者可能难以与散发性PD患者区分。单基因原因包括常染色体显性（SNCA，LRRK 2，VPS 35，EIF 4G 1）以及receptor（PARK 2，PINK 1，DJ-1）遗传突变。帕金森综合征的其他隐性形式存在非典型体征，包括极早期疾病发作、肌张力障碍、痴呆和锥体束征。寻找表型相关基因的新技术（下一代测序，全基因组关联研究）扩大了单基因PD和改变PD风险的变体的范围。风险基因的实例包括两种溶酶体酶编码基因GBA和SMPD 1，它们分别与PD风险增加5倍和9倍相关。人们希望进一步了解PD的遗传组成将允许设计改变疾病进程的治疗方法。
The discovery of genes implicated in familial forms of Parkinson's disease (PD) has provided new insights into the molecular events leading to neurodegeneration. Clinically, patients with genetically determined PD can be difficult to distinguish from those with sporadic PD. Monogenic causes include autosomal dominantly (SNCA, LRRK2, VPS35, EIF4G1) as well as recessively (PARK2, PINK1, DJ-1) inherited mutations. Additional recessive forms of parkinsonism present with atypical signs, including very early disease onset, dystonia, dementia and pyramidal signs. New techniques in the search for phenotype-associated genes (next-generation sequencing, genome-wide association studies) have expanded the spectrum of both monogenic PD and variants that alter risk to develop PD. Examples of risk genes include the two lysosomal enzyme coding genes GBA and SMPD1, which are associated with a 5-fold and 9-fold increased risk of PD, respectively. It is hoped that further knowledge of the genetic makeup of PD will allow designing treatments that alter the course of the disease.