National Centre for Rare Diseases, Undiagnosed Rare Diseases Interdepartmental Unit, Istituto Superiore di Sanità, Rome, Italy.
Department of Educational Science, University of Catania, Catania, Italy.
Ital J Pediatr. 2020 Sep 14;46(1):130. doi: 10.1186/s13052-020-00883-8.
For a number of persons with rare diseases (RDs) a definite diagnosis remains undiscovered with relevant physical, psychological and social consequences. Undiagnosed RDs (URDs) require other than specialised clinical centres, outstanding molecular investigations, common protocols and dedicated actions at national and international levels; thus, many "Undiagnosed RDs programs" have been gradually developed on the grounds of a well-structured multidisciplinary approach.
The Italian Undiagnosed Rare Diseases Network (IURDN) was established in 2016 to improve the level of diagnosis of persons with URD living in Italy. Six Italian Centres of Expertise represented the network. The National Centre for Rare Diseases at the Istituto Superiore di Sanità coordinates the whole project. The software PhenoTips was used to collect the information of the clinical cases.
One hundred and ten cases were analysed between March 2016 and June 2019. The age of onset of the diseases ranged from prenatal age to 51 years. Conditions were predominantly sporadic; almost all patients had multiple organs involvements. A total of 13/71 family cases were characterized by WES; in some families more than one individual was affected, so leading to 20/71 individuals investigated. Disease causing variants were identified in two cases and were associated to previously undescribed phenotypes. In 5 cases, new candidate genes were identified, although confirmatory tests are pending. In three families, investigations were not completed due to the scarce compliance of members and molecular investigations were temporary suspended. Finally, three cases (one familial) remain still unsolved. Twelve undiagnosed clinical cases were then selected to be shared at International level through PhenomeCentral in accordance to the UDNI statement.
Our results showed a molecular diagnostic yield of 53,8%; this value is comparable to the diagnostic rates reported in other international studies. Cases collected were also pooled with those collected by UDNI International Network. This represents a unique example of global initiative aimed at sharing and validating knowledge and experience in this field. IURDN is a multidisciplinary and useful initiative linking National and International efforts aimed at making timely and appropriate diagnoses in RD patients who still do not have a confirmed diagnosis even after a long time.
对于许多患有罕见病（RD）的人来说，他们的疾病仍然无法确诊，这给他们带来了身体、心理和社会方面的负面影响。对于这些未确诊的 RD（URD）患者，除了需要专业的临床中心、卓越的分子研究、通用的方案外，还需要国家和国际层面的专门行动，因此，许多“未确诊罕见病计划”逐渐基于完善的多学科方法得以发展。
意大利未确诊罕见病网络（IURDN）成立于 2016 年，旨在提高意大利 URD 患者的诊断水平。该网络由六个意大利专业中心组成，国家罕见病中心在意大利卫生研究院协调整个项目。使用 PhenoTips 软件收集临床病例信息。
2016 年 3 月至 2019 年 6 月，共分析了 110 例病例。疾病的发病年龄从胎儿期到 51 岁不等。这些疾病大多为散发性疾病；几乎所有患者都有多个器官受累。共对 13/71 个家族病例进行了 WES 分析；在一些家庭中，有不止一个人受到影响，因此共对 71 名个体进行了调查。在 2 例病例中发现了致病变异，这些变异与之前未描述的表型相关。在 5 例病例中，确定了新的候选基因，但确认性测试仍在进行中。在 3 个家庭中，由于成员的配合度较低，分子研究暂时中止。最后，3 例（1 例为家族性）仍未得到解决。然后，根据 UDNI 声明，选择了 12 例未确诊的临床病例通过 PhenomeCentral 在国际层面上进行共享。
我们的研究结果显示，分子诊断率为 53.8%；这一数值与其他国际研究报告的诊断率相当。收集的病例还与 UDNI 国际网络收集的病例进行了汇总。这是全球倡议的一个独特例子，旨在分享和验证该领域的知识和经验。IURDN 是一个多学科的有益举措，将国家和国际的努力联系起来，旨在为那些即使经过长时间仍未确诊的 RD 患者做出及时和适当的诊断。
