家族性特发性震颤与5号染色体q35区域的连锁关系。

Linkage of familial essential tremor to chromosome 5q35.

作者信息

Hicks James E, Konidari Ioanna, Scott Burton L, Stajich Jeffrey M, Ashley-Koch Allison E, Gilbert John R, Scott William K

机构信息

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.

出版信息

Mov Disord. 2016 Jul;31(7):1059-62. doi: 10.1002/mds.26582. Epub 2016 Feb 26.

DOI:10.1002/mds.26582

PMID:26918299

Abstract

BACKGROUND

Essential tremor is a neurological condition characterized by tremor during voluntary movement. To date, 3 loci linked to familial essential tremor have been identified.

METHODS

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.

RESULTS

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.

CONCLUSION

摘要

背景

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。

方法

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。