Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological?
Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological?
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DOI：
10.1002/humu.21284
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发表时间：
2010-07
期刊：
影响因子：
3.9
通讯作者：
Stankiewicz, Pawel
中科院分区：
文献类型：
--
作者：
Szafranski, Przemyslaw;Schaaf, Christian P.;Person, Richard E.;Gibson, Ian B.;Xia, Zhilian;Mahadevan, Sangeetha;Wiszniewska, Joanna;Bacino, Carlos A.;Lalani, Seema;Potocki, Lorraine;Kang, Sung-Hae;Patel, Ankita;Cheung, Sau Wai;Probst, Frank J.;Graham, Brett H.;Shinawi, Marwan;Beaudet, Arthur L.;Stankiewicz, Pawel
我们对临床芯片检测到的涉及CHRNA7基因的15q13.2-q13.3处的4个~1.6-Mb微重复和55个较小的350-680-kb微重复进行了研究。应用高分辨率阵列-CGH，我们定位了这些微复制的全部118个染色体断裂点。我们还对聚集在非等位基因同源重组热点(Nahr)的26个微小重复断裂点进行了测序。所有四个大的微复制可能由Nahr在BP4和BP5 LCR之间产生，54个小的微复制可能由Nahr在两个CHRNA7-LCR之间产生。我们鉴定了两类~1.6-Mb微复制和五类复制大小不同的小微复制，并表明它们复制了整个CHRNA7。我们认为，小分子复制之间的大小差异是由于常见的BP4-BP5倒位的异质性造成的。11例涉及CHRNA7的微小微重复的患者的临床数据和家族史表明，这些微重复可能与发育迟缓/智力低下、肌肉张力低下和各种神经精神疾病有关。然而，我们得出的结论是，这些微复制和它们相关的烟碱型乙酰胆碱受体α7亚单位剂量增加的可能性目前尚不确定。然而，如果它们被证明具有病理效应，它们的高频率可能会使它们成为许多神经行为障碍的共同风险因素。
We have investigated four ~1.6-Mb microduplications and 55 smaller 350–680-kb microduplications at 15q13.2–q13.3 involving the CHRNA7 gene that were detected by clinical microarray analysis. Applying high-resolution array-CGH, we mapped all 118 chromosomal breakpoints of these microduplications. We also sequenced 26 small microduplication breakpoints that were clustering at hotspots of nonallelic homologous recombination (NAHR). All four large microduplications likely arose by NAHR between BP4 and BP5 LCRs, and 54 small microduplications arose by NAHR between two CHRNA7-LCR copies. We identified two classes of ~1.6-Mb microduplications and five classes of small microduplications differing in duplication size, and show that they duplicate the entire CHRNA7. We propose that size differences among small microduplications result from preexisting heterogeneity of the common BP4–BP5 inversion. Clinical data and family histories of 11 patients with small microduplications involving CHRNA7 suggest that these microduplications might be associated with developmental delay/mental retardation, muscular hypotonia, and a variety of neuropsychiatric disorders. However, we conclude that these microduplications and their associated potential for increased dosage of the CHRNA7-encoded α7 subunit of nicotinic acetylcholine receptors are of uncertain clinical significance at present. Nevertheless, if they prove to have a pathological effects, their high frequency could make them a common risk factor for many neurobehavioral disorders.
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影响因子：
4
作者：
Miller DT;Shen Y;Weiss LA;Korn J;Anselm I;Bridgemohan C;Cox GF;Dickinson H;Gentile J;Harris DJ;Hegde V;Hundley R;Khwaja O;Kothare S;Luedke C;Nasir R;Poduri A;Prasad K;Raffalli P;Reinhard A;Smith SE;Sobeih MM;Soul JS;Stoler J;Takeoka M;Tan WH;Thakuria J;Wolff R;Yusupov R;Gusella JF;Daly MJ;Wu BL
通讯作者：
Wu BL
影响因子：
30.8
作者：
Helbig I;Mefford HC;Sharp AJ;Guipponi M;Fichera M;Franke A;Muhle H;de Kovel C;Baker C;von Spiczak S;Kron KL;Steinich I;Kleefuss-Lie AA;Leu C;Gaus V;Schmitz B;Klein KM;Reif PS;Rosenow F;Weber Y;Lerche H;Zimprich F;Urak L;Fuchs K;Feucht M;Genton P;Thomas P;Visscher F;de Haan GJ;Møller RS;Hjalgrim H;Luciano D;Wittig M;Nothnagel M;Elger CE;Nürnberg P;Romano C;Malafosse A;Koeleman BP;Lindhout D;Stephani U;Schreiber S;Eichler EE;Sander T
通讯作者：
Sander T
影响因子：
5.3
作者：
El-Hattab AW;Smolarek TA;Walker ME;Schorry EK;Immken LL;Patel G;Abbott MA;Lanpher BC;Ou Z;Kang SH;Patel A;Scaglia F;Lupski JR;Cheung SW;Stankiewicz P
通讯作者：
Stankiewicz P
染色体微阵列分析的临床实施：2513例产后病例的摘要。
影响因子：
3.7
作者：
Lu, Xinyan;Shaw, Chad A.;Patel, Ankita;Li, Jiangzhen;Cooper, M. Lance;Wells, William R.;Sullivan, Cathy M.;Sahoo, Trilochan;Yatsenko, Svetlana A.;Bacino, Carlos A.;Stankiewicz, Pawel;Ou, Zhishu;Chinault, A. Craig;Beaudet, Arthur L.;Lupski, James R.;Cheung, Sau W.;Ward, Patricia A.
通讯作者：
Ward, Patricia A.
影响因子：
4
作者：
Ben-Shachar S;Lanpher B;German JR;Qasaymeh M;Potocki L;Nagamani SC;Franco LM;Malphrus A;Bottenfield GW;Spence JE;Amato S;Rousseau JA;Moghaddam B;Skinner C;Skinner SA;Bernes S;Armstrong N;Shinawi M;Stankiewicz P;Patel A;Cheung SW;Lupski JR;Beaudet AL;Sahoo T
通讯作者：
Sahoo T