Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.
Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.
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DOI：
10.1186/1471-2350-12-106
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发表时间：
2011-08-09
影响因子：
--
通讯作者：
Zweier C
中科院分区：
文献类型：
--
作者：
Gregor A;Albrecht B;Bader I;Bijlsma EK;Ekici AB;Engels H;Hackmann K;Horn D;Hoyer J;Klapecki J;Kohlhase J;Maystadt I;Nagl S;Prott E;Tinschert S;Ullmann R;Wohlleber E;Woods G;Reis A;Rauch A;Zweier C
CNTNAP2和NRXN1的杂合拷贝数和错义变异反复与广泛的神经精神疾病相关，如发育性语言和自闭症谱系障碍、癫痫和精神分裂症。近年来，有报道称任何一种基因的纯合或复合杂合缺陷可导致严重的智力残疾。对99例重度智力残疾、与皮特-霍普金斯综合征相似和/或疑似隐性遗传的患者进行CNTNAP2和NRXN1基因突变筛查。对45例患者进行分子核型分析。在另外8例CNTNAP2或NRXN1杂合缺失的可变智力残疾患者中，对剩余等位基因进行测序。通过对一组重度智障患者CNTNAP2和NRXN1的分子核型和突变筛选，我们在1例患者中发现了NRXN1的杂合缺失，在4例患者中分别发现了CNTNAP2的剪接位点、移码和停止突变。无论是在这些患者中，还是在另外8名NRXN1或CNTNAP2中存在杂合缺失的患者中，我们都无法确定第二个等位基因上的缺陷。NRXN1基因的一个缺失和CNTNAP2基因的一个缺失是从头发生的，在另一个家庭中，有学习困难的母亲也发现了这种缺失，在所有其他测试家庭中，父母中有一方被证明是各自缺失或突变的健康携带者。我们报道了与严重智力残疾相关的CNTNAP2或NRXN1杂合缺陷患者，而以前仅报道过隐性缺陷。这些结果扩大了两种基因杂合缺陷患者的表型严重程度。严重感染患者和轻度感染或无症状携带者父母之间的巨大差异可能表明存在第二种打击，不一定位于同一基因。
Heterozygous copy-number and missense variants in CNTNAP2 and NRXN1 have repeatedly been associated with a wide spectrum of neuropsychiatric disorders such as developmental language and autism spectrum disorders, epilepsy and schizophrenia. Recently, homozygous or compound heterozygous defects in either gene were reported as causative for severe intellectual disability. 99 patients with severe intellectual disability and resemblance to Pitt-Hopkins syndrome and/or suspected recessive inheritance were screened for mutations in CNTNAP2 and NRXN1. Molecular karyotyping was performed in 45 patients. In 8 further patients with variable intellectual disability and heterozygous deletions in either CNTNAP2 or NRXN1, the remaining allele was sequenced. By molecular karyotyping and mutational screening of CNTNAP2 and NRXN1 in a group of severely intellectually disabled patients we identified a heterozygous deletion in NRXN1 in one patient and heterozygous splice-site, frameshift and stop mutations in CNTNAP2 in four patients, respectively. Neither in these patients nor in eight further patients with heterozygous deletions within NRXN1 or CNTNAP2 we could identify a defect on the second allele. One deletion in NRXN1 and one deletion in CNTNAP2 occurred de novo, in another family the deletion was also identified in the mother who had learning difficulties, and in all other tested families one parent was shown to be healthy carrier of the respective deletion or mutation. We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before. These results expand the spectrum of phenotypic severity in patients with heterozygous defects in either gene. The large variability between severely affected patients and mildly affected or asymptomatic carrier parents might suggest the presence of a second hit, not necessarily located in the same gene.
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影响因子：
158.5
作者：
Strauss, KA;Puffenberger, EG;Morton, DH
通讯作者：
Morton, DH
DOI：
10.1002/ajmg.b.31063
发表时间：
2010-06-05
影响因子：
2.8
作者：
Ching, Michael S. L.;Shen, Yiping;Tan, Wen-Hann;Jeste, Shafali S.;Morrow, Eric M.;Chen, Xiaoli;Mukaddes, Nahit M.;Yoo, Seung-Yun;Hanson, Ellen;Hundley, Rachel;Austin, Christina;Becker, Ronald E.;Berry, Gerard T.;Driscoll, Katherine;Engle, Elizabeth C.;Friedman, Sandra;Gusella, James F.;Hisama, Fuki M.;Irons, Mira B.;Lafiosca, Tina;LeClair, Elaine;Miller, David T.;Neessen, Michael;Picker, Jonathan D.;Rappaport, Leonard;Rooney, Cynthia M.;Sarco, Dean P.;Stoler, Joan M.;Walsh, Christopher A.;Wolff, Robert R.;Zhang, Ting;Nasir, Ramzi H.;Wu, Bai-Lin
通讯作者：
Wu, Bai-Lin
DOI：
10.1056/nejmoa0802828
发表时间：
2008-11-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
Vernes SC;Newbury DF;Abrahams BS;Winchester L;Nicod J;Groszer M;Alarcón M;Oliver PL;Davies KE;Geschwind DH;Monaco AP;Fisher SE
通讯作者：
Fisher SE
影响因子：
9.8
作者：
Arking, Dan E.;Cutler, David J.;Chakravarti, Aravinda
通讯作者：
Chakravarti, Aravinda
影响因子：
16.2
作者：
Poliak, S;Gollan, L;Peles, E
通讯作者：
Peles, E