17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report.
17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report.
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DOI：
10.1186/s12881-017-0479-3
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发表时间：
2017-10-25
影响因子：
--
通讯作者：
El-Hattab AW
中科院分区：
文献类型：
--
作者：
Wessel K;Suleiman J;Khalaf TE;Kishore S;Rolfs A;El-Hattab AW
涉及17q23的染色体重排很少被描述。据报道，在发育迟缓和生长迟缓的个体中存在17q23.1q23.2的缺失，而17q23.1q23.2的重复似乎与内翻足分离。位于17q23.2的TBX2和TBX4基因的剂量改变被认为是导致17q23.1q23.2缺失和重复的个体出现表型的原因。在本报告中，我们报告了一名儿童的临床表型，该儿童在TBX2和TBX4区域远端17q23.2q23.3处出现了以前未报道的新生重复。我们报告一个7.5岁的男孩，他有言语和语言障碍、学习困难、协调障碍、精细运动技能障碍、脑电图异常的罕见癫痫发作和行为障碍（轻度自残、多动-注意力不集中和刻板的手部运动）。染色体微阵列显示染色体17q23.2q23.3存在2 mb的重复。父母双方都没有重复，这表明这种重复在孩子身上是从头开始的。复制区域包含16个基因。这可能是增加剂量的一个或多个基因在这个区域负责观察到的表型。TANC2基因是位于重复区域的基因之一。它编码TANC（四肽重复序列，锚蛋白重复序列和含卷曲线圈）家族的一个成员，包括TANC1和TANC2。这些蛋白在大脑中高度表达，在突触调节中起重要作用。因此，提示TANC2可能是导致所观察到的表型的候选基因，因为增加TANC2剂量可能会改变突触，导致神经元功能障碍和在17q23.2q23.3重复的儿童中观察到的神经行为表型。
Chromosomal rearrangements involving 17q23 have been described rarely. Deletions at 17q23.1q23.2 have been reported in individuals with developmental delay and growth retardation, whereas duplications at 17q23.1q23.2 appear to segregate with clubfoot. Dosage alterations in the TBX2 and TBX4 genes, located in 17q23.2, have been proposed to be responsible for the phenotypes observed in individuals with 17q23.1q23.2 deletions and duplications. In this report, we present the clinical phenotype of a child with a previously unreported de novo duplication at 17q23.2q23.3 located distal to the TBX2 and TBX4 region. We report a 7.5-year-old boy with speech and language disorder, learning difficulties, incoordination, fine motor skill impairment, infrequent seizures with abnormal EEG, and behavior disturbances (mild self-inflicted injuries, hyperactivity-inattention, and stereotyped hand movements). Chromosomal microarray revealed a 2-Mb duplication of chromosome 17q23.2q23.3. Both parents did not have the duplication indicating that this duplication is de novo in the child. The duplicated region encompasses 16 genes. It is possible that increased dosage of one or more genes in this region is responsible for the observed phenotype. The TANC2 gene is one of the genes in the duplicated region.It encodes a member of the TANC (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing) family which includes TANC1 and TANC2. These proteins are highly expressed in brain and play major roles in synapsis regulation. Hence, it is suggestive that TANC2 is the likely candidate gene responsible for the observed phenotype as an increased TANC2 dosage can potentially alter synapsis, resulting in neuronal dysfunction and the neurobehavioral phenotype observed in this child with 17q23.2q23.3 duplication.
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影响因子：
9.8
作者：
Miller, David T.;Adam, Margaret P.;Ledbetter, David H.
通讯作者：
Ledbetter, David H.
影响因子：
9.8
作者：
Ballif, Blake C.;Theisen, Aaron;Shaffer, Lisa G.
通讯作者：
Shaffer, Lisa G.
影响因子：
30.8
作者：
Weraarpachai, Woranontee;Antonicka, Hana;Shoubridge, Eric A.
通讯作者：
Shoubridge, Eric A.
影响因子：
4
作者：
El-Hattab, Ayman W.;Fang, Ping;Cheung, Sau Wai
通讯作者：
Cheung, Sau Wai
影响因子：
4.1
作者：
Xiang, Bixia;Zhu, Hongbo;Fan, Yao-Shan
通讯作者：
Fan, Yao-Shan