Contactin 4 as an autism susceptibility locus.
Contactin 4 as an autism susceptibility locus.
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DOI：
10.1002/aur.184
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发表时间：
2011-06
期刊：
影响因子：
4.7
通讯作者：
Herman, Gail E.
中科院分区：
文献类型：
--
作者：
Cottrell, Catherine E.;Bir, Natalie;Varga, Elizabeth;Alvarez, Carlos E.;Bouyain, Samuel;Zernzach, Randall;Thrush, Devon L.;Evans, Johnna;Trimarchi, Michael;Butter, Eric M.;Cunningham, David;Gastier-Foster, Julie M.;McBride, Kim L.;Herman, Gail E.
接触蛋白（CNTN）和接触蛋白相关蛋白（CNTNAP）基因家族中与神经发育障碍（包括自闭症）相关的几个成员的结构和序列变异已经被描述。利用阵列比较基因组杂交（CGH）技术，我们在一名自闭症患者的接触蛋白4基因（CNTN4） 5 '端3p26.3处发现了一个约535 kb的遗传缺失。基于这一发现和先前关于CNTN4在自闭症谱系障碍（ASD）和3p -微缺失综合征中基因组重排的报道，我们在一个局部ASD队列中对该基因的编码区进行了测序，并与一组对照组进行了比较。在4/75无血缘关系的ASD患者和1/107对照中发现了独特的错义变异。所有的氨基酸替换都是非同义的，发生在进化上保守的位置，因此，感觉可能是有害的。然而，这些数据并没有达到统计学意义，也没有在所有的ASD家族中变异与疾病分离。最后，在体外实验中，两种变体与相互作用蛋白PTPRG的结合没有可检测到的差异。因此，需要更大规模的研究来确定CNTN4是否与其他遗传和/或环境因素一起作为自闭症易感位点发挥作用。
Structural and sequence variation have been described in several members of the contactin (CNTN) and contactin associated protein (CNTNAP) gene families in association with neurodevelopmental disorders, including autism. Using array comparative genome hybridization (CGH), we identified a maternally inherited ~535 kb deletion at 3p26.3 encompassing the 5′ end of the contactin 4 gene (CNTN4) in a patient with autism. Based on this finding and previous reports implicating genomic rearrangements of CNTN4 in autism spectrum disorders (ASDs) and 3p− microdeletion syndrome, we undertook sequencing of the coding regions of the gene in a local ASD cohort in comparison with a set of controls. Unique missense variants were identified in 4/75 unrelated individuals with an ASD, as well as in 1/107 controls. All of the amino acid substitutions were nonsynonomous, occurred at evolutionarily conserved positions, and were, thus, felt likely to be deleterious. However, these data did not reach statistical significance, nor did the variants segregate with disease within all of the ASD families. Finally, there was no detectable difference in binding of two of the variants to the interacting protein PTPRG in vitro. Thusadditional, larger studies will be necessary to determine whether CNTN4 functions as an autism susceptibility locus in combination with other genetic and/or environmental factors.
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影响因子：
56.9
作者：
Morrow, Eric M.;Yoo, Seung-Yun;Flavell, Steven W.;Kim, Tae-Kyung;Lin, Yingxi;Hill, Robert Sean;Mukaddes, Nahit M.;Balkhy, Soher;Gascon, Generoso;Hashmi, Asif;Al-Saad, Samira;Ware, Janice;Joseph, Robert M.;Greenblatt, Rachel;Gleason, Danielle;Ertelt, Julia A.;Apse, Kira A.;Bodell, Adria;Partlow, Jennifer N.;Barry, Brenda;Yao, Hui;Markianos, Kyriacos;Ferland, Russell J.;Greenberg, Michael E.;Walsh, Christopher A.
通讯作者：
Walsh, Christopher A.
影响因子：
16.2
作者：
Kaneko-Goto, Tomomi;Yoshihara, Sei-ichi;Yoshihara, Yoshihiro
通讯作者：
Yoshihara, Yoshihiro
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
9.8
作者：
Li, Bingshan;Leal, Suzanne M.
通讯作者：
Leal, Suzanne M.
影响因子：
5.8
作者：
Larkin, M. A.;Blackshields, G.;Higgins, D. G.
通讯作者：
Higgins, D. G.