El Bouchikhi Ihssane, Belhassan Khadija, Moufid Fatima Zohra, Iraqui Houssaini Mohammed, Bouguenouch Laila, Samri Imane, Atmani Samir, Ouldim Karim
Medical Genetics and Oncogenetics Laboratory, HASSAN II University Hospital, BP 1835, Atlas, Fez 30000, Morocco.
Laboratory of Microbial Biotechnology, Faculty of Sciences and Techniques, University of Sidi Mohammed Ben Abdellah, B.P. 2202, Route d'Imouzzer, Fez 30000, Morocco.
Int J Pediatr Adolesc Med. 2016 Dec;3(4):133-142. doi: 10.1016/j.ijpam.2016.06.003. Epub 2016 Aug 18.
Noonan syndrome is a common autosomal dominant disorder characterized by short stature, congenital heart disease and facial dysmorphia with an incidence of 1/1000 to 2500 live births. Up to now, several genes have been proven to be involved in the disturbance of the transduction signal through the RAS-MAP Kinase pathway and the manifestation of Noonan syndrome. The first gene described was , followed by , , , , , , and , and recently , , and , among others. Progressively, the physiopathology and molecular etiology of most signs of Noonan syndrome have been demonstrated, and inheritance patterns as well as genetic counseling have been established. In this review, we summarize the data concerning clinical features frequently observed in Noonan syndrome, and then, we describe the molecular etiology as well as the physiopathology of most Noonan syndrome-causing genes. In the second part of this review, we assess the mutational rate of Noonan syndrome-causing genes reported up to now in most screening studies. This review should give clinicians as well as geneticists a full view of the molecular aspects of Noonan syndrome and the authentic prevalence of the mutational events of its causing-genes. It will also facilitate laying the groundwork for future molecular diagnosis research, and the development of novel treatment strategies.
努南综合征是一种常见的常染色体显性疾病，其特征为身材矮小、先天性心脏病和面部畸形，发病率为1/1000至2500活产儿。到目前为止，已证实有几个基因参与了通过RAS-MAP激酶途径的信号转导紊乱以及努南综合征的表现。第一个被描述的基因是 ，随后是 、 、 、 、 、 和 ，最近还有 、 和 等。逐渐地，努南综合征大多数体征的病理生理学和分子病因已得到证实，并且遗传模式以及遗传咨询也已确立。在本综述中，我们总结了有关努南综合征中经常观察到的临床特征的数据，然后，我们描述了大多数导致努南综合征的基因的分子病因以及病理生理学。在本综述的第二部分，我们评估了迄今为止大多数筛查研究中报道的导致努南综合征的基因的突变率。本综述应为临床医生和遗传学家提供努南综合征分子方面的全面视图及其致病基因突变事件的真实患病率。它还将有助于为未来的分子诊断研究奠定基础，并开发新的治疗策略。
