Sara Scaccini, Carlo Alberto Cesaroni, Stefano Giuseppe Caraffi, Susanna Rizzi, Simonetta Rosato, Francesca Peluso, Carlotta Spagnoli, Anna Cavalli, Chiara Brugnoli, Giulia Scandolo, Agnese Pantani, Ivan Ivanovski, Livia Garavelli, Daniele Frattini, Carlo Fusco
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引用次数: 0
摘要
ADNP相关疾病[以前称为Helsmoortel-Van der Aa综合征(HVDAS)]是一种罕见的遗传疾病,由活动依赖性神经保护剂同源盒(ADNP)基因突变引起。ADNP蛋白具有多种功能,包括作为大脑发育的重要转录因子。此外,ADNP的致病变异已被认为是自闭症谱系障碍(ASD)和智力残疾最常见的单基因原因之一。临床特征包括颅面畸形、先天性心脏缺陷、胃肠问题,如进食困难、胃食管反流和频繁呕吐、视力问题、反复感染和癫痫发作。在这里,我们描述了一个新颖的案例,一个女孩在婴儿期引起了我们的注意,因为她的运动技能很差,而且是刻板的,重复的无目的的动作,还有智力残疾。全外显子组测序显示ADNP基因的新杂合变异,导致5岁时诊断为HVDAS。12岁时,神经传导速度测试显示严重的四肢轴突运动多发性神经病。在本文中,我们希望关注与致病性ADNP新生变异相关的周围神经系统受累的存在,这可能有助于ADNP相关疾病的临床特征。
Axonal motor polyneuropathy in a 13 years old Girl with a de Novo variant in ADNP.
ADNP-Related Disorder [previously known as Helsmoortel-Van der Aa syndrome (HVDAS)] is a rare genetic condition resulting from mutations in the activity-dependent neuroprotector homeobox (ADNP) gene. The ADNP protein has multiple functions, including serving as an essential transcription factor for brain development. In addition, pathogenic variants in ADNP have been recognized as one of the most frequent monogenic causes of autism spectrum disorder (ASD) and intellectual disability. Clinical features include craniofacial dysmorphisms, congenital heart defects, gastrointestinal problems such as feeding difficulties, gastroesophageal reflux and frequent vomiting, vision problems, recurrent infections and seizures. Here we describe the novel case of a girl who came to our attention in infancy because of poor and stereotyped motor repertoire, repetitive purposeless movements, and intellectual disability. Whole exome sequencing revealed a de novo heterozygous variant in the ADNP gene, leading to the diagnosis of HVDAS at age 5 years. At the age of 12, nerve conduction velocity testing showed severe four-limb axonal motor polyneuropathy. In this article, we would like to focus on the presence of peripheral nervous system involvement associated with the pathogenic ADNP de novo variant, which may contribute to the clinical characterization of ADNP-Related Disorder.
期刊介绍:
Neurogenetics publishes findings that contribute to a better understanding of the genetic basis of normal and abnormal function of the nervous system. Neurogenetic disorders are the main focus of the journal. Neurogenetics therefore includes findings in humans and other organisms that help understand neurological disease mechanisms and publishes papers from many different fields such as biophysics, cell biology, human genetics, neuroanatomy, neurochemistry, neurology, neuropathology, neurosurgery and psychiatry.
All papers submitted to Neurogenetics should be of sufficient immediate importance to justify urgent publication. They should present new scientific results. Data merely confirming previously published findings are not acceptable.