快速发作的肥胖伴下丘脑功能障碍,通气不足和自主神经失调(ROHHAD)是一种罕见的,危及生命,病因不明的儿科疾病,由于对临床表现的了解不足,其诊断困难,缺乏任何验证性测试。患有ROHHAD的儿童通常表现为快速发作的体重增加,可能会被随访,几个月或几年,下丘脑功能障碍,通气不足,自主神经功能障碍,包括肠动力受损,和神经嵴起源的肿瘤。尽管罗哈德缺乏遗传证据,近年来进行了几项研究,探索了可能的遗传起源,结果不成功。为了扩大对可能的遗传风险因素的搜索,试图分析两个三重奏中的非编码变体(先证者与父母),在热那亚(意大利)的Gaslini儿童医院招募。两个病人都是女性,具有典型的罗哈德历史。基因变异(单核苷酸变异,短插入/删除,搜索了两个先证者之间共有的剪接变体或均聚片段的串联扩增)或改变的基因组区域(拷贝数变异或结构变体)。目前,我们没有发现任何潜在的致病变化,与ROHHAD临床表型一致,涉及基因,两个三重奏之间共享的区域或路径。为了明确排除遗传病因,第三代测序技术(例如,长读数测序,光学映射)应应用,以及其他途径,包括与免疫和自身免疫性疾病相关的疾病,应该探索,不仅利用基因组学,而且利用不同的基因组数据集。
Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (
ROHHAD) is a rare, life-threatening, pediatric disorder of unknown etiology, whose diagnosis is made difficult by poor knowledge of clinical manifestation, and lack of any confirmatory tests. Children with
ROHHAD usually present with rapid onset weight gain which may be followed, over months or years, by hypothalamic dysfunction, hypoventilation, autonomic dysfunction, including impaired bowel motility, and tumors of neural crest origin. Despite the lack of evidence of inheritance in
ROHHAD, several studies have been conducted in recent years that have explored possible genetic origins, with unsuccessful results. In order to broaden the search for possible genetic risk factors, an attempt was made to analyse the non-coding variants in two trios (proband with parents), recruited in the Gaslini Children\'s Hospital in Genoa (Italy). Both patients were females, with a typical history of
ROHHAD. Gene variants (single nucleotide variants, short insertions/deletions, splice variants or in tandem expansion of homopolymeric tracts) or altered genomic regions (copy number variations or structural variants) shared between the two probands were searched. Currently, we have not found any potentially pathogenic changes, consistent with the
ROHHAD clinical phenotype, and involving genes, regions or pathways shared between the two trios. To definitively rule out the genetic etiology, third-generation sequencing technologies (e.g., long-reads sequencing, optical mapping) should be applied, as well as other pathways, including those associated with immunological and autoimmune disorders, should be explored, making use not only of genomics but also of different -omic datasets.