复合杂合parkin基因突变家族的不同表型  

Heterogeneous phenotype in a family with compound heterozygous parkin gene mutations

作　　者：Hunter C.B. J. Jankovic 邱伟庆 

机构地区：[1]Department of Neurology, aylor College of Medicine, 6550 Fannin St, Houston, TX 77030, United States Dr.

出　　处：《世界核心医学期刊文摘（神经病学分册）》2006年第6期17-18,共2页Digest of the World Core Medical Journals:Clinical Neurology

摘　　要：Background: Mutations in the parkin gene （PRKN） cause autosomal recessive early-onset Parkinson disease （EOPD）. Objective: To investigate the presence of mutations in the PRKN gene in a white family with EOPD and the genotype-phenotype correlations. Design: Twenty me mbers belonging to 3 generations of the EOPD fam ily with 4 affected subjects underwent genetic analysis. Direct genomic DNA sequ encing, semi-quantitative polymerase chain reaction, real-time quantitative po lymerase chain reaction, and reverse-transcriptase polymerase chain reaction an alyses were performed to identify the PRKN mutation. Results: Compound heterozyg ous mutations （T240M and EX 56 del） in the PRKN gene were identified in 4 patie nts with early onset （at ages 30-38 years）.Although heterozygous T240M and homo zygous EX 56 del mutations in the PRKN gene have been previously described,this is, to our knowledge, the first report of these mutations in compound heterozyg otes. The phenotype of patients was that of classic autosomal recessive EOPD cha racterized by beneficial response to levodopa, relatively slow progression,and m otor complications. All heterozygous mutation carriers （T240M or EX 56 del） and a 56-year-old woman who was a compound heterozygou s mutation carrier （T240M and EX 56 del） were free of any neurological symptoms . Conclusions:Compound heterozygous mutations （T240M and EX56 del） in the PRKN gene were found to cause autosomal recessive EOPD in 4 members of a large white family. One additional member with the same mutation, who is more than 10 years older than the mean age at onset of the 4 affected individuals, had no clinical manifestation of the disease. This incomplete penetrance has implications for ge netic counseling, and it suggests that complex gene-environment interactions ma y play a role in the pathogenesis of PRKN EOPD.Background： Mutations in the parkin gene （PRKN） cause autosomal recessive early-onset Parkinson disease （EOPD）. Objective： To investigate the presence of mutations in the PRKN gene in a white family with EOPD and the genotype-phenotype correlations. Design： Twenty me mbers belonging to 3 generations of the EOPD family with 4 affected subjects underwent genetic analysis. Direct genomic DNA sequencing, semi-quantitative polymerase chain reaction, real-time quantitative polymerase chain reaction, and reverse-transcriptase polymerase chain reaction analyses were performed to identify the PRKN mutation. Results： Compound heterozygous mutations （T240M and EX 56 del） in the PRKN gene were identified in 4 patients with early onset （at ages 30- 38 years） . Although heterozygous T240M and homozygous EX 5-6 del mutations in the PRKN gene have been previously described, this is, to our knowledge, the first report of these mutations in compound heterozygotes. The phenotype of patients was that of classic autosomal recessive EOPD characterized by beneficial response to levodopa, relatively slow progression, and motor complications. All heterozygous mutation carriers （T240M or EX 5_6 del） and a 56-year-old woman who was a compound heterozygous mutation carrier （T240M and EX 5_6 del） were free of any neurological symptoms. Conclusions： Compound heterozygous mutations （T240M and EX5_6 del） in the PRKN gene were found to cause autosomal recessive EOPD in 4 members of a large white family. One additional member with the same mutation, who is more than 10 years older than the mean age at onset of the 4 affected individuals, had no clinical manifestation ofthe disease. This incomplete penetrance has implications for genetic counseling, and it suggests that complex gene-environment interactions may play a role in the pathogenesis of PRKN EOPD.

关 键 词：PARKIN基因突变 表型关系 杂合 常染色体隐性遗传性 家族 复合 半定量聚合酶链反应 实时定量聚合酶链反应 PARKIN基因 基因携带者 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R746.4[医药卫生—临床医学]