Hicks James E, Konidari Ioanna, Scott Burton L, Stajich Jeffrey M, Ashley-Koch Allison E, Gilbert John R, Scott William K
John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Mov Disord. 2016 Jul;31(7):1059-62. doi: 10.1002/mds.26582. Epub 2016 Feb 26.
Essential tremor is a neurological condition characterized by tremor during voluntary movement. To date, 3 loci linked to familial essential tremor have been identified.
We examined 48 essential tremor patients in 5 large essential tremor pedigrees in our data set for genetic linkage using an Affymetrix Axiom array. Linkage analysis was performed using an affecteds-only dominant model in SIMWALK2. To incorporate all genotype information, GERMLINE was used to identify genome segments shared identical-by-descent in pairs of affecteds. Exome sequencing was performed in pedigrees showing evidence of linkage.
For one family, chromosomes 5 and 18 showed genome-wide significant linkage to essential tremor. Shared segment analysis excluded the 18p11 candidate region and reduced the 5q35 region by 1 megabase. Exome sequencing did not identify a potential causative variant in this region.
A locus on chromosome 5 is linked to essential tremor. Further research is needed to identify a causative variant. © 2016 International Parkinson and Movement Disorder Society.
特发性震颤是一种以随意运动时出现震颤为特征的神经系统疾病。迄今为止，已确定了3个与家族性特发性震颤相关的基因座。
我们使用Affymetrix Axiom芯片，对数据集中5个大型特发性震颤家系中的48例特发性震颤患者进行了基因连锁分析。在SIMWALK2中使用仅受累者显性模型进行连锁分析。为纳入所有基因型信息，使用GERMLINE来识别受累者对中通过血缘相同的共享基因组片段。对显示有连锁证据的家系进行外显子组测序。
对于一个家系，5号和18号染色体显示出全基因组范围与特发性震颤的显著连锁。共享片段分析排除了18p11候选区域，并将5q35区域缩小了1兆碱基。外显子组测序未在该区域鉴定出潜在的致病变异。
5号染色体上的一个基因座与特发性震颤相关。需要进一步研究以鉴定致病变异。©2016国际帕金森病和运动障碍协会。
