Reuter Miriam S, Krumbiegel Mandy, Schlüter Gregor, Ekici Arif B, Reis André, Zweier Christiane
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
MVZ Prenatal Medicine, Gynecology and Genetics, Nürnberg, Germany.
Am J Med Genet A. 2017 Aug;173(8):2231-2234. doi: 10.1002/ajmg.a.38288. Epub 2017 May 24.
Non-recurrent deletions in 2q24.1, minimally overlapping two genes, NR4A2 and GPD2, were recently described in individuals with language impairment and behavioral and cognitive symptoms. We herewith report on a female patient with a similar phenotype of severe language and mild cognitive impairment, in whom we identified a de novo deletion covering only NR4A2. NR4A2 encodes a transcription factor highly expressed in brain regions critical for speech and language and implicated in dopaminergic neuronal development. Our findings of a de novo deletion of NR4A2 in an individual with mild intellectual disability and prominent speech and language impairment provides further evidence for NR4A2 haploinsufficiency being causative for neurodevelopmental and particularly language phenotypes.
最近有报道称，2q24.1区域存在非复发性缺失，该区域最少重叠两个基因，即NR4A2和GPD2，这些缺失出现在有语言障碍以及行为和认知症状的个体中。我们在此报告一名患有严重语言障碍和轻度认知障碍相似表型的女性患者，在该患者中我们发现了一个仅覆盖NR4A2的新生缺失。NR4A2编码一种转录因子，该转录因子在对言语和语言至关重要的脑区中高度表达，并与多巴胺能神经元发育有关。我们在一名患有轻度智力障碍以及明显言语和语言障碍的个体中发现了NR4A2的新生缺失，这一发现进一步证明了NR4A2单倍剂量不足是神经发育尤其是语言表型的病因。
