{"title":"Genetic factors in the etiology of idiopathic Parkinson's disease.","authors":"P Vieregge","doi":"10.1007/BF02250916","DOIUrl":null,"url":null,"abstract":"<p><p>Overshadowed by a vigorous search for an environmentally-derived toxin that would be possibly relevant for the pathogenesis of idiopathic Parkinson's disease (PD), genetic factors have largely been neglected for this condition during the last two decades. Recent descriptions of kindreds over three or more generations with several family members affected have renewed the interest in genetics of PD. Concurring with this, diagnostic concepts and pathologic criteria for PD and for idiopathic Lewy-body (LB) disease have been reevaluated such that LB-proven parkinsonism is sufficiently differentiated from familial parkinsonism without LB pathology. Surveys on genetic epidemiology in PD have confirmed the 19th century's notion that 10 to 15% of PD index cases report a further family member with PD. These figures were, however, substantiated on a statistical basis only in single surveys when comparisons were made with the numbers of PD relatives in control index cases. Twin studies did not reveal a higher rate of concordance within monozygotic pairs than in dizygotic pairs. Tests of striatal 18-F-Dopa uptake in clinically unaffected mono- and dizygotic co-twins did not alter the ratio between the concordance rates. Though not excluded by the twin studies, multifactorial (or polygenic) inheritance as well as mitochondrial inheritance are at present less likely to cover most of the inheritance pattern in familial LB parkinsonism. Instead, autosomal dominant inheritance with reduced penetrance is the most probable inheritance pattern for most of the reported pedigrees. Molecular genetic investigations have to consider the biochemical basis of the age- and region-specific pathology of PD. The first analyses of linkage and allelic associations gave inconclusive results in sporadic and familial PD. The hunt for metabolic factors that link geno- and phenotype expression in PD will continue.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"8 1-2","pages":"1-37"},"PeriodicalIF":0.0000,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02250916","citationCount":"42","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/BF02250916","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 42
Abstract
Overshadowed by a vigorous search for an environmentally-derived toxin that would be possibly relevant for the pathogenesis of idiopathic Parkinson's disease (PD), genetic factors have largely been neglected for this condition during the last two decades. Recent descriptions of kindreds over three or more generations with several family members affected have renewed the interest in genetics of PD. Concurring with this, diagnostic concepts and pathologic criteria for PD and for idiopathic Lewy-body (LB) disease have been reevaluated such that LB-proven parkinsonism is sufficiently differentiated from familial parkinsonism without LB pathology. Surveys on genetic epidemiology in PD have confirmed the 19th century's notion that 10 to 15% of PD index cases report a further family member with PD. These figures were, however, substantiated on a statistical basis only in single surveys when comparisons were made with the numbers of PD relatives in control index cases. Twin studies did not reveal a higher rate of concordance within monozygotic pairs than in dizygotic pairs. Tests of striatal 18-F-Dopa uptake in clinically unaffected mono- and dizygotic co-twins did not alter the ratio between the concordance rates. Though not excluded by the twin studies, multifactorial (or polygenic) inheritance as well as mitochondrial inheritance are at present less likely to cover most of the inheritance pattern in familial LB parkinsonism. Instead, autosomal dominant inheritance with reduced penetrance is the most probable inheritance pattern for most of the reported pedigrees. Molecular genetic investigations have to consider the biochemical basis of the age- and region-specific pathology of PD. The first analyses of linkage and allelic associations gave inconclusive results in sporadic and familial PD. The hunt for metabolic factors that link geno- and phenotype expression in PD will continue.
在过去的二十年里,由于对一种可能与特发性帕金森病(PD)发病机制有关的环境来源毒素的大力研究,遗传因素在很大程度上被忽视了。最近对三代或三代以上家族成员患病的描述重新引起了人们对帕金森病遗传学的兴趣。与此同时,PD和特发性路易体病(LB)的诊断概念和病理标准已被重新评估,从而使LB证实的帕金森病与没有LB病理的家族性帕金森病充分区分开来。帕金森病的遗传流行病学调查证实了19世纪的观点,即10 - 15%的帕金森病指数病例报告有其他家庭成员患有帕金森病。然而,当与对照指数病例中PD亲属的数量进行比较时,这些数字仅在统计基础上得到证实。双生子研究并没有显示同卵对的一致性比异卵对高。在临床未受影响的单卵双胞胎和异卵双胞胎中,纹状体18- f -多巴摄取试验没有改变一致性率之间的比率。虽然没有被双胞胎研究排除,但多因子(或多基因)遗传以及线粒体遗传目前不太可能涵盖家族性LB帕金森病的大部分遗传模式。相反,外显率降低的常染色体显性遗传是大多数报道的谱系中最可能的遗传模式。分子遗传学研究必须考虑PD的年龄和区域特异性病理的生化基础。对散发性和家族性帕金森病的连锁和等位基因关联的首次分析没有给出确定的结果。寻找PD中与基因和表型表达相关的代谢因子将继续进行。