Miranda Debora M, Wigg Karen, Kabia E Mameisia, Feng Yu, Sandor Paul, Barr Cathy L
Department of Pharmacology of Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 5;150B(4):483-6. doi: 10.1002/ajmg.b.30840.
Previously the Slit and Trk-like family member 1 (SLITRK1) gene was identified as a candidate gene for Gilles de la Tourette Syndrome (GTS) based on a patient that carried a chromosomal inversion on 13q, as well as the identification of two rare DNA variants in the SLITRK1 gene. Since that report, studies have tested for the two rare variants in GTS and either did not find them, or when found, they did not segregate with the disorder in families, casting doubt on the relationship of this gene to GTS. We tested for these two rare variants and genotyped three polymorphisms that tag the currently identified major haplotypes of this gene in a sample of 154 nuclear families with GTS. In addition, the entire coding region was screened for novel DNA variants. We did not find the two reported rare variants in any of the probands or siblings in these families. We did however find significant evidence for association of a single polymorphism and of haplotypes of the three tagging polymorphisms. These findings provide the first support for the original finding indicating SLITRK1 as a susceptibility gene for GTS and indicate that further study of this gene in GTS is warranted.
此前，基于一名携带13号染色体倒位的患者以及在Slit和Trk样家族成员1（SLITRK1）基因中发现的两种罕见DNA变异，该基因被确定为抽动秽语综合征（GTS）的候选基因。自该报告发表以来，多项研究对GTS患者中的这两种罕见变异进行了检测，结果要么未发现它们，要么即便发现了，这些变异在家族中也未与该疾病共分离，这使得人们对该基因与GTS之间的关系产生了怀疑。我们在一个由154个患有GTS的核心家庭组成的样本中，对这两种罕见变异进行了检测，并对标记该基因当前已确定的主要单倍型的三个多态性位点进行了基因分型。此外，我们还对整个编码区进行了新型DNA变异的筛查。在这些家庭的任何先证者或其兄弟姐妹中，我们均未发现所报道的这两种罕见变异。然而，我们确实发现了一个单核苷酸多态性位点以及三个标记多态性位点的单倍型存在显著关联的证据。这些发现为最初表明SLITRK1是GTS易感基因的研究结果提供了首个支持，并表明有必要对该基因在GTS中的作用进行进一步研究。
