ROHHAD（Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation）是一种罕见的、威胁患儿生命的疾病，其病因尚未明确，临床表现知识匮乏，也缺乏任何确诊试验，因此诊断困难。ROHHAD患儿通常表现为急速增重，可能在数月或数年后出现下丘脑功能障碍、低通气、自主功能异常（包括肠动力障碍）以及神经嵴原性肿瘤。尽管ROHHAD没有遗传证据，但近年来已进行了多项研究，探索了可能的遗传起源，但结果并不成功。为了扩大对可能的遗传风险因素的搜寻范围，我们尝试分析在意大利Genoa的Gaslini儿童医院招募的两个三联体（患者和其父母）的非编码变异。这两个患者均为女性，表现出典型的ROHHAD病史。我们搜索了两个患者之间共享的基因变异（单核苷酸变异、短插入/缺失、剪接变异或串联扩展的同型多聚轨迹）或改变的基因组区域（拷贝数变异或结构变异）。目前，我们尚未发现任何与ROHHAD临床表型一致且涉及到两个三联体共享的基因、区域或通路的潜在致病性变化。为了最终排除遗传病因，应该应用第三代测序技术（如长读测序、光学映射），并探索与免疫和自身免疫疾病相关的其他通路，不仅利用基因组学，还应利用不同的"组学"数据集。版权所有©2023 Grossi, Rusmini, Cusano, Massidda, Santamaria, Napoli, Angelelli, Fava, Uva, Ceccherini和Maghnie。

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.Copyright © 2023 Grossi, Rusmini, Cusano, Massidda, Santamaria, Napoli, Angelelli, Fava, Uva, Ceccherini and Maghnie.