Genomics and Human Genetics Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco; Laboratory of Physiopathology, Molecular Genetics & Biotechnology, Faculty of Sciences Ain Chock, Health and Biotechnology Research Centre, Hassan II University of Casablanca, Maarif B.P, 5366, Casablanca, Morocco.
Genomics and Human Genetics Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco; Université Angers, MitoLab Team, UMR CNRS 6015, INSERM U1083, Institut MitoVasc, SFR ICAT, Angers, France; Team of Anthropogenetics and Biotechnologies, Faculty of Sciences, Chouaïb Doukkali University, El Jadida, Morocco.
Eur J Med Genet. 2022 Jun;65(6):104515. doi: 10.1016/j.ejmg.2022.104515. Epub 2022 Apr 27.
Intellectual disability is characterized by a significant impaired intellectual and adaptive functioning, affecting approximately 1-3% of the population, which can be caused by a variety of environmental and genetic factors. In this respect, de novo heterozygous HECW2 variants were associated recently with neurodevelopmental disorders associated to hypotonia, seizures, and absent language. HECW2 encodes an E3 ubiquitin-protein ligase that stabilizes and enhances transcriptional activity of p73, a key factor regulating proliferation, apoptosis, and neuronal differentiation, which are together essential for proper brain development. Here, using whole exome sequencing, we identified a homozygous nonsense HECW2 variant: c.736C > T; p.Arg246* in a proband from a Moroccan consanguineous family, with developmental delay, intellectual disability, hypotonia, generalized tonico-clonic seizures and a persistent tilted head. Thus this study describes the first homozygous HECW2 variant, inherited as an autosomal recessive pattern, contrasting with former reported de novo variants found in HECW2 patients.
智力障碍的特征是明显的智力和适应功能受损，影响大约 1-3%的人口，这可能是由各种环境和遗传因素引起的。在这方面，最近新发现的杂合 HECW2 变异与神经发育障碍有关，这些障碍与张力减退、癫痫发作和语言缺失有关。HECW2 编码一种 E3 泛素蛋白连接酶，可稳定和增强 p73 的转录活性，p73 是调节增殖、凋亡和神经元分化的关键因子，这些因子对于正常的大脑发育是必不可少的。在这里，我们使用全外显子组测序，在一名来自摩洛哥近亲家庭的先证者中发现了一个纯合无义 HECW2 变异：c.736C>T; p.Arg246*，该先证者患有发育迟缓、智力障碍、张力减退、全身性强直阵挛性癫痫发作和持续倾斜的头部。因此，本研究描述了第一个纯合 HECW2 变异，以常染色体隐性遗传模式遗传，与以前报道的 HECW2 患者中发现的新发现的杂合变异形成对比。
