Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size.
Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size.
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DOI：
10.1136/jmg.2009.073015
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发表时间：
2010-05
影响因子：
4
通讯作者：
Lupski JR
中科院分区：
文献类型：
--
作者：
Shinawi M;Liu P;Kang SH;Shen J;Belmont JW;Scott DA;Probst FJ;Craigen WJ;Graham BH;Pursley A;Clark G;Lee J;Proud M;Stocco A;Rodriguez DL;Kozel BA;Sparagana S;Roeder ER;McGrew SG;Kurczynski TW;Allison LJ;Amato S;Savage S;Patel A;Stankiewicz P;Beaudet AL;Cheung SW;Lupski JR
最近，16p11.2的缺失和相互重复与自闭症和发育迟缓有关。我们在所有提交给临床阵列-CGH(比较基因组杂交)分析的样本中发现了16p11.2的27个缺失和18个重复。对17名缺失受试者和10名复制受试者进行了详细的分子和表型特征分析。17例缺失者和10例重复者最常见的临床表现是言语/语言延迟和认知障碍。缺失患者的其他表型包括运动延迟(50%)、癫痫(~40%)、行为问题(~40%)、先天性畸形(~30%)和自闭症(~20%)。重复患者的表型包括运动延迟(6/10)、行为问题(特别是注意缺陷多动障碍(ADHD))(6/10)、先天性异常(5/10)和癫痫(3/10)。16p11.2缺失的患者有统计学意义的大头畸形(p<；0.0017)，10个重复的患者中有6个有小头畸形。一个缺失的受试者没有症状，另一个重复的受试者具有正常的认知和行为表型。基因组分析揭示了16p11.2区域的额外复杂性和机制含义。在有父母研究的10例缺失病例中，除2例外，所有病例的染色体重排都是从头开始的。此外，2例新发病例在分析的血样中出现明显的嵌合体缺失。在有数据的10例重复病例中，有5例观察到3例新生病例和2例遗传性病例。重复的相互作用16p11.2缺失和复制以一系列主要的神经认知表型为特征，这些表型受到不完全外显和可变表达的影响。在重复患者中观察到的自闭症和缺失的大头畸形以及ADHD和小头畸形支持了自闭症谱和精神病谱的直径模型，即基因组姐妹疾病的行为表型。
Deletion and the reciprocal duplication in 16p11.2 were recently associated with autism and developmental delay. We indentified 27 deletions and 18 duplications of 16p11.2 were identified in 0.6% of all samples submitted for clinical array-CGH (comparative genomic hybridisation) analysis. Detailed molecular and phenotypic characterisations were performed on 17 deletion subjects and ten subjects with the duplication. The most common clinical manifestations in 17 deletion and 10 duplication subjects were speech/language delay and cognitive impairment. Other phenotypes in the deletion patients included motor delay (50%), seizures (~40%), behavioural problems (~40%), congenital anomalies (~30%), and autism (~20%). The phenotypes among duplication patients included motor delay (6/10), behavioural problems (especially attention deficit hyperactivity disorder (ADHD)) (6/10), congenital anomalies (5/10), and seizures (3/10). Patients with the 16p11.2 deletion had statistically significant macrocephaly (p<0.0017) and 6 of the 10 patients with the duplication had microcephaly. One subject with the deletion was asymptomatic and another with the duplication had a normal cognitive and behavioural phenotype. Genomic analyses revealed additional complexity to the 16p11.2 region with mechanistic implications. The chromosomal rearrangement was de novo in all but 2 of the 10 deletion cases in which parental studies were available. Additionally, 2 de novo cases were apparently mosaic for the deletion in the analysed blood sample. Three de novo and 2 inherited cases were observed in the 5 of 10 duplication patients where data were available. Recurrent reciprocal 16p11.2 deletion and duplication are characterised by a spectrum of primarily neurocognitive phenotypes that are subject to incomplete penetrance and variable expressivity. The autism and macrocephaly observed with deletion and ADHD and microcephaly seen in duplication patients support a diametric model of autism spectrum and psychotic spectrum behavioural phenotypes in genomic sister disorders.
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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
DOI：
10.1006/bbrc.1995.1062
发表时间：
1995-01-17
影响因子：
3.1
作者：
ORITA, S;SASAKI, T;TAKAI, Y
通讯作者：
TAKAI, Y
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
影响因子：
4
作者：
Menten, B.;Maas, N.;Vermeesch, J. R.
通讯作者：
Vermeesch, J. R.