Missense and truncating variants in CHD5 in a dominant neurodevelopmental disorder with intellectual disability, behavioral disturbances, and epilepsy.
Missense and truncating variants in CHD5 in a dominant neurodevelopmental disorder with intellectual disability, behavioral disturbances, and epilepsy.
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具有智力障碍，行为障碍和癫痫病的主要神经发育障碍中CHD5中的错义和截断变体。
DOI：
10.1007/s00439-021-02283-2
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发表时间：
2021-07
期刊：
影响因子：
5.3
通讯作者：
Mignot C
中科院分区：
文献类型：
--
作者：
Parenti I;Lehalle D;Nava C;Torti E;Leitão E;Person R;Mizuguchi T;Matsumoto N;Kato M;Nakamura K;de Man SA;Cope H;Shashi V;Undiagnosed Diseases Network;Friedman J;Joset P;Steindl K;Rauch A;Muffels I;van Hasselt PM;Petit F;Smol T;Le Guyader G;Bilan F;Sorlin A;Vitobello A;Philippe C;van de Laar IMBH;van Slegtenhorst MA;Campeau PM;Au PYB;Nakashima M;Saitsu H;Yamamoto T;Nomura Y;Louie RJ;Lyons MJ;Dobson A;Plomp AS;Motazacker MM;Kaiser FJ;Timberlake AT;Fuchs SA;Depienne C;Mignot C
chromodomain helicase DNA-binding protein 5（CHD 5）基因位于关键的1 p36微缺失区，编码神经元发育所需的核小体重塑和去乙酰化（NuRD）复合物的亚基。九个染色体结构域（CHD）基因中的六个致病性变体导致常染色体显性遗传神经发育障碍，而CHD 5相关疾病仍然未知。多亏了GeneMatcher和国际合作，我们组建了一个由16个携带杂合CHD 5变异体的无关个体组成的队列，所有这些变异体都是通过外显子组测序鉴定的。12例患者有新发CHD 5变异，包括10个错义和2个剪接位点变异。三个家族性病例有无意义或错义变异分离与语言延迟，学习障碍，和/或颅缝早闭。一名患者携带移码变异的未知遗传，由于父亲的不可用。最常见的临床特征包括语言障碍（81%）、行为症状（69%）、智力障碍（64%）、癫痫（62%）和运动延迟（56%）。癫痫类型是可变的，在3名患者中观察到West综合征，在2名患者中观察到全身强直阵挛性癫痫发作，在1名患者中观察到其他亚型。我们的研究结果表明，与其他CHD相关疾病一致，杂合子CHD 5变体与可变的神经发育综合征相关，其中包括以言语延迟，癫痫和行为问题为主要特征的智力残疾。在线版本包含补充材料，可通过10.1007/s 00439 -021-02283-2获得。
Located in the critical 1p36 microdeletion region, the chromodomain helicase DNA-binding protein 5 (CHD5) gene encodes a subunit of the nucleosome remodeling and deacetylation (NuRD) complex required for neuronal development. Pathogenic variants in six of nine chromodomain (CHD) genes cause autosomal dominant neurodevelopmental disorders, while CHD5-related disorders are still unknown. Thanks to GeneMatcher and international collaborations, we assembled a cohort of 16 unrelated individuals harboring heterozygous CHD5 variants, all identified by exome sequencing. Twelve patients had de novo CHD5 variants, including ten missense and two splice site variants. Three familial cases had nonsense or missense variants segregating with speech delay, learning disabilities, and/or craniosynostosis. One patient carried a frameshift variant of unknown inheritance due to unavailability of the father. The most common clinical features included language deficits (81%), behavioral symptoms (69%), intellectual disability (64%), epilepsy (62%), and motor delay (56%). Epilepsy types were variable, with West syndrome observed in three patients, generalized tonic–clonic seizures in two, and other subtypes observed in one individual each. Our findings suggest that, in line with other CHD-related disorders, heterozygous CHD5 variants are associated with a variable neurodevelopmental syndrome that includes intellectual disability with speech delay, epilepsy, and behavioral problems as main features. The online version contains supplementary material available at 10.1007/s00439-021-02283-2.
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DOI：
10.1016/j.mrfmmm.2006.07.012
发表时间：
2007-05-01
影响因子：
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作者：
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