Identification of chromosome abnormalities in subtelomeric regions by microarray analysis: a study of 5,380 cases.
Identification of chromosome abnormalities in subtelomeric regions by microarray analysis: a study of 5,380 cases.
复制标题
DOI：
10.1002/ajmg.a.32399
复制
发表时间：
2008-09-01
影响因子：
2
通讯作者：
Cheung, Sau W.
中科院分区：
文献类型：
--
作者：
Shao, Lina;Shaw, Chad A.;Lu, Xin-Yan;Sahoo, Trilochan;Bacino, Carlos A.;Lalani, Seema R.;Stankiewicz, Pawel;Yatsenko, Svetlana A.;Li, Yinfeng;Neill, Sarah;Pursley, Amber N.;Chinault, A. Craig;Patel, Ankita;Beaudet, Arthur L.;Lupski, James R.;Cheung, Sau W.
亚端粒失衡是先天性疾病的重要原因。这些异常的筛选传统上利用GTG显带分析，荧光原位杂交（FISH）测定，和多重连接依赖的探针扩增。基于微阵列的比较基因组杂交（阵列CGH）是一种相对较新的技术，可以识别显微和亚显微染色体不平衡。已经提出，在亚端粒区域具有扩展覆盖的阵列可以在单个实验中更有效地表征亚端粒畸变。由贝勒医学院开发的用于染色体微阵列分析（CMA）的靶向阵列平均具有12个BAC/PAC克隆，覆盖41个亚端粒区域中的每一个的10 Mb。我们使用CMA筛选了5，380名连续的临床患者。转诊的最常见原因包括发育迟缓（DD）和/或精神发育迟滞（MR）、畸形特征（DF）、多发性先天性异常（MCA）、癫痫发作障碍（SD）和自闭症或其他行为异常。我们在236例患者（4.4%）中发现了端粒下区域的致病性重排。在这些患者中，103例有缺失，58例有重复，44例有不平衡易位，31例有复杂重排。染色体核型分析正常者（2.98%）、异常者（43.4%）、未进行或未进行染色体核型分析者（3.16%）的检出率各不相同。278例患者中有6例先前正常的亚端粒-FISH分析显示异常，包括间质缺失，两个末端缺失，两个间质重复和一个末端重复。总之，端粒下区域的基因组失衡对先天性疾病有显着影响。具有延伸的亚端粒区域覆盖范围（高达10 Mb）的靶向阵列CGH将增强亚端粒失衡的检测，特别是亚显微失衡。
Subtelomeric imbalances are a significant cause of congenital disorders. Screening for these abnormalities has traditionally utilized GTG-banding analysis, fluorescence in situ hybridization (FISH) assays, and multiplex ligation-dependent probe amplification. Microarray-based comparative genomic hybridization (array-CGH) is a relatively new technology that can identify microscopic and submicroscopic chromosomal imbalances. It has been proposed that an array with extended coverage at subtelomeric regions could characterize subtelomeric aberrations more efficiently in a single experiment. The targeted arrays for chromosome microarray analysis (CMA), developed by Baylor College of Medicine, have on average 12 BAC/PAC clones covering 10 Mb of each of the 41 subtelomeric regions. We screened 5,380 consecutive clinical patients using CMA. The most common reasons for referral included developmental delay (DD), and/or mental retardation (MR), dysmorphic features (DF), multiple congenital anomalies (MCA), seizure disorders (SD), and autistic, or other behavioral abnormalities. We found pathogenic rearrangements at subtelomeric regions in 236 patients (4.4%). Among these patients, 103 had a deletion, 58 had a duplication, 44 had an unbalanced translocation, and 31 had a complex rearrangement. The detection rates varied among patients with a normal karyotype analysis (2.98%), with an abnormal karyotype analysis (43.4%), and with an unavailable or no karyotype analysis (3.16%). Six patients out of 278 with a prior normal subtelomere-FISH analysis showed an abnormality including an interstitial deletion, two terminal deletions, two interstitial duplications, and a terminal duplication. In conclusion, genomic imbalances at subtelomeric regions contribute significantly to congenital disorders. Targeted array-CGH with extended coverage (up to 10 Mb) of subtelomeric regions will enhance the detection of subtelomeric imbalances, especially for submicroscopic imbalances.
登录
查看更多内容
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：
2
作者：
Adeyinka, A;Adams, SA;Jalal, SM
通讯作者：
Jalal, SM
影响因子：
3.6
作者：
Bar-Shira, Anat;Rosner, Guy;Orr-Urtreger, Avi
通讯作者：
Orr-Urtreger, Avi
影响因子：
2
作者：
Aradhya, Swaroop;Manning, Melanie A.;Cherry, Athena M.
通讯作者：
Cherry, Athena M.
影响因子：
4
作者：
Menten, B.;Maas, N.;Vermeesch, J. R.
通讯作者：
Vermeesch, J. R.