Tourette disorder spectrum maps to chromosome 14q31.1 in an Italian kindred.
Tourette disorder spectrum maps to chromosome 14q31.1 in an Italian kindred.
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DOI：
10.1007/s10048-010-0244-7
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发表时间：
2010-10
期刊：
影响因子：
2.2
通讯作者：
Bonifati, Vincenzo
中科院分区：
文献类型：
--
作者：
Breedveld, Guido J.;Fabbrini, Giovanni;Oostra, Ben A.;Berardelli, Alfredo;Bonifati, Vincenzo
抽动秽语综合征（TS）是一种常见的神经精神疾病，病因不明。在连锁研究中，许多染色体区域被指定为TS基因座，但确认的成功有限，致病突变尚未明确确定。此外，TS，慢性抽搐，强迫症（OCD）发生在TS亲属之间的频率增加，支持这些表型代表相同的遗传决定谱的一部分的观点。我们确定了一个四代分离TS，慢性多发性运动抽搐（CMT）和强迫症的意大利家族，我们进行了10厘摩（cM）的全基因组连锁扫描，以映射潜在的遗传缺陷。在常染色体显性模型和较窄的表型定义（仅TS和CMT受试者被视为受影响）下，通过仅受影响分析检测到与染色体14q31.1（多点LOD = 2.4）的暗示性连锁。当采用更广泛的表型定义（TS、CMT和OCD受试者被视为受影响）时，连锁峰增加，接近全基因组显著性（LOD = 3.29）。单倍型分析确定了一个2.3 cM的关键区域，共享的所有亲属与TS，CMT，或强迫症。总之，我们提供了强有力的证据连锁TS频谱染色体14q31.1。在最近的TS同胞对扫描中报告了与染色体14 q重叠区域的暗示连锁。因此，该区域可能包含TS的重要基因，应优先进行进一步研究。本文的在线版本（doi：10.1007/s10048-010-0244-7）包含补充材料，可供授权用户使用。
Tourette syndrome (TS) is a frequent neuropsychiatric disorder of unknown etiology. A number of chromosomal regions have been nominated as TS loci in linkage studies, but confirmation has met with limited success and causative mutations have not yet been definitely identified. Furthermore, TS, chronic tics, and obsessive–compulsive disorder (OCD) occur at increased frequencies among TS relatives, supporting the view that these phenotypes represent parts of the same genetically determined spectrum. We ascertained a four-generation Italian kindred segregating TS, chronic multiple motor tics (CMT), and OCD, and we performed a ten-centimorgan (cM) genome-wide linkage scan in order to map the underlying genetic defect. Suggestive linkage to chromosome 14q31.1 (multipoint LOD = 2.4) was detected by affected-only analysis under an autosomal dominant model and a narrower phenotype definition (only the subjects with TS and CMT were considered as affected). The linkage peak increased and it approached genome-wide significance (LOD = 3.29) when a broader phenotype definition was adopted (subjects with TS, CMT, and OCD considered as affected). Haplotype analysis defined a ∼2.3 cM critical region, shared by all the relatives with TS, CMT, or OCD. In conclusion, we provide strong evidence for linkage of TS spectrum to chromosome 14q31.1. Suggestive linkage to an overlapping region of chromosome 14q was reported in a recent scan of TS sibling pairs. This region might therefore contain an important gene for TS, and it should be prioritized for further study. The online version of this article (doi:10.1007/s10048-010-0244-7) contains supplementary material, which is available to authorized users.
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