Tourette syndrome (TS) is a complex neurodevelopmental disorder (NDD) characterized by multiple chronic involuntary motor and vocal tics with onset during childhood or adolescence. Most TS patients present with additional comorbidities, typically attention deficit hyperactivity disorder (ADHD), obsessive- compulsive disorder (OCD), autism spectrum disorder (ASD) and intellectual disability (ID). Both TS and ID are genetically complex disorders that likely occur as a result of the effects of multiple genes interacting with other environmental factors. In addition to single gene mutations and chromosomal disorders, copy number variations (CNVs) are implicated across many NDDs and ID and contribute to their shared genetic etiology. Screening of CNVs using microarray-based Comparative Genomic Hybridization (aCGH) is now routinely performed in all subjects with NDD and ID. We report a case of a 12-year-old girl diagnosed with Gilles de la Tourette Syndrome associated to behavior disorders and intellectual disability in particular with regard to language. Array-CGH analysis showed a CNV of a subtelomeric region Xq28 (gain of 260 kb) inherited from the healthy father. The duplication contains two genes, VAMP7 and SPRY3 of the PAR2 pseudoautosomal region. FISH analysis revealed that the duplicated segment is located on the short arm of a chromosome 13, resulting in a trisomy of the region. In the proband the expression levels of the genes evaluated in the peripheral blood sample are comparable both those of the mother and to those of female control subjects. Although the trisomy of the 260 kb region from Xq28 identified in proband is also shared by the healthy father, it is tantalizing to speculate that, together with genetic risk factors inherited from the mother, it may play a role in the development of a form of Tourette syndrome with intellectual disability. This hypothesis is also supported by the fact that both genes present in the duplicated region (VAMP7 and SPRY3) are expressed in the CNS and are implicated in neurotransmission and neurite growth and branching. In addition, similar CNVs have been identified in individuals whose phenotype is associated with autism spectrum disorders or intellectual disability.

中文翻译：

---

在患有 Gilles de la Tourette 综合征和智力障碍的受试者中遗传的伪常染色体区域 Xq28 的重复：病例报告。

抽动秽语综合征 (TS) 是一种复杂的神经发育障碍 (NDD)，其特征是在儿童期或青春期发病的多种慢性非自主运动和发声抽搐。大多数 TS 患者存在其他合并症，通常是注意力缺陷多动障碍 (ADHD)、强迫症 (OCD)、自闭症谱系障碍 (ASD) 和智力障碍 (ID)。TS 和 ID 都是遗传上复杂的疾病，可能是由于多个基因与其他环境因素相互作用的结果而发生的。除了单基因突变和染色体疾病外，拷贝数变异 (CNV) 还涉及许多 NDD 和 ID，并有助于它们共同的遗传病因。使用基于微阵列的比较基因组杂交 (aCGH) 筛选 CNVs 现在在所有患有 NDD 和 ID 的受试者中常规进行。我们报告了一例被诊断患有 Gilles de la Tourette 综合征的 12 岁女孩，该病例与行为障碍和智力障碍有关，尤其是在语言方面。Array-CGH 分析显示从健康父亲遗传的亚端粒区域 Xq28（增加 260 kb）的 CNV。重复包含 PAR2 假常染色体区域的两个基因 VAMP7 和 SPRY3。FISH 分析显示，重复片段位于 13 号染色体的短臂上，导致该区域的三体性。在先证者中，外周血样本中评估的基因表达水平与母亲和女性对照受试者的表达水平相当。尽管在先证者中发现的来自 Xq28 的 260 kb 区域的三体性也为健康的父亲所共有，但很有可能推测它与遗传自母亲的遗传风险因素一起，可能在一种形式的发育中发挥作用。图雷特综合征伴智力障碍。这一假设也得到了以下事实的支持：复制区域中存在的两个基因（VAMP7 和 SPRY3）都在 CNS 中表达，并且与神经传递和神经突生长和分支有关。此外，在表型与自闭症谱系障碍或智力障碍相关的个体中也发现了类似的 CNV。与从母亲那里遗传的遗传风险因素一起，它可能在某种形式的智力障碍图雷特综合征的发展中发挥作用。这一假设也得到了以下事实的支持：复制区域中存在的两个基因（VAMP7 和 SPRY3）都在 CNS 中表达，并且与神经传递和神经突生长和分支有关。此外，在表型与自闭症谱系障碍或智力障碍相关的个体中也发现了类似的 CNV。与从母亲那里遗传的遗传风险因素一起，它可能在某种形式的智力障碍图雷特综合征的发展中发挥作用。这一假设也得到了以下事实的支持：复制区域中存在的两个基因（VAMP7 和 SPRY3）都在 CNS 中表达，并且与神经传递和神经突生长和分支有关。此外，在表型与自闭症谱系障碍或智力障碍相关的个体中也发现了类似的 CNV。