Undiagnosed Diseases: Italy-US Collaboration and International Efforts to Tackle Rare and Common Diseases Lacking a Diagnosis

Taruscio, Domenica; Floridia, Giovanna; Salvatore, Marco; Groft, Stephen C.; Gahl, William A.

doi:10.1007/978-3-319-67144-4_2

Cited by 25 publications

(20 citation statements)

References 4 publications

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“…Inspired by the UDN, the UDNI has built a consensus framework of principles, governance and best practices [7]. After the establishment of the NIH-UDP in the United States [5], other UDP initiatives have been launched in some European countries (Austria, Bulgaria, Hungary, Sweden, Italy and Spain) and in other continents (Japan, Korea, Australia and Canada) [8]. The emergence of undiagnosed RD programs has coincided with the expansion of next-generation sequencing technologies.…”

Section: Introductionmentioning

confidence: 99%

SpainUDP: The Spanish Undiagnosed Rare Diseases Program

López-Martín

Martı́nez-Delgado

Bermejo‐Sánchez

et al. 2018

IJERPH

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One of the IRDiRC goals for 2017–2027 is to achieve definitive diagnosis for rare undiagnosed diseases within one year, as delay in diagnosis remains one of the pending issues in the rare diseases field. The Spanish Undiagnosed Rare Diseases Program (SpainUDP) was created in response to this challenging scenario to cover patients’ needs and after seeing the success of the Undiagnosed Diseases Program (UDP) in the USA. SpainUDP offers a multidisciplinary approach to those patients who have long sought a diagnosis without any success. During the first phase of the protocol, undiagnosed cases are sent to SpainUDP by individual patients or families, patient organizations or hospitals. After careful analysis of phenotype, data from sequencing experiments (WES) is processed with a standard pipeline and detailed standardized phenotypic information (mapped to the Human Phenotype Ontology, HPO) is connected to genetic data. In addition, the participation of SpainUDP in international initiatives such as the European projects RD-Connect and Solve RD, the Undiagnosed Diseases Network International (UDNI), and the MatchMaker Exchange (MME) platform, allows the establishment of a global data sharing strategy across multiple projects submitting data to these international initiatives. From the official beginning of the program (at the end of 2015) until early 2018, 147 cases were accepted in SpainUDP. During this time, 37 cases (25%) dropped out the program due to several reasons. The remaining 110 cases are distributed as follows: phenotypic and genotypic (WES) characterization was finished in 30 cases, of which 20 (67%) were diagnosed; 21 cases are pending on variants’ validation by Sanger sequencing; in 25 cases, WES is ongoing and 34 cases are being studied for deep phenotypic characterization. In conclusion, SpainUDP aims to achieve a diagnosis following two recommendations of the IRDiRC: the patients’ diagnosis in as short a time as possible and the promotion of data sharing (especially genomic) at the international level.

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Section: Introductionmentioning

confidence: 99%

SpainUDP: The Spanish Undiagnosed Rare Diseases Program

López-Martín

Martı́nez-Delgado

Bermejo‐Sánchez

et al. 2018

IJERPH

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“…Researchers on rare diseases have emphasized the need for the integration of rare disease plans and studies into international consortiums. This would replace the fragmented approach currently in place with a more coordinated effort that would include larger numbers of patients and caregivers (46)(47)(48).…”

Section: Collaborationsmentioning

confidence: 99%

A compilation of national plans, policies and government actions for rare diseases in 23 countries

Khosla

Valdéz

2018

IRDR

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Previous studies have focused on the comparison of specific laws among multiple countries and regions; for example, laws related to facilitating treatments with orphan drugs or laws seeking to address the multiple needs of patients with rare diseases. The purpose of this scoping review is to examine and compare published reports on national plans, polices and legislation related to all rare diseases in different countries. We also examine strategies or programs that countries may have for these diseases. Articles were obtained from journals and books published between January 1, 2000, through December 15, 2017. Reports from the grey literature (documents issued by government and private organizations) were included if they were available on the internet. The databases used were Google and Google Scholar, PubMed, and the websites of Orphanet and the National Organization for Rare Disorders (NORD). We obtained information on 23 countries. Among these countries, the way in which rare diseases were defined varied from having similar definitions to no definition. Multinational programs supported by common or similar laws are likely to have a greater impact on rare diseases than single country programs.

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“…Rare disease is a health condition that affects a small number of people compared with other prevalent diseases in the general population (Baldovino, Moliner, Taruscio, Daina, & Roccatello, ). To date, between 5,000 and 8,000 distinct rare diseases have been documented with new ones reported regularly in the medical literature (Taruscio, Floridia, Salvatore, Groft, & Gahl, ). Although they are characterized by their rarity, the total number of patients affected is large [e.g., 25–50 millions in the United States (Fernandez‐Marmiesse, Gouveia, & Couce, ), 27–36 millions in the EU (Moliner & Waligora, ), and 16.8 millions in China (Yang, Su, Lee, & Bai, )].…”

Section: Introductionmentioning

confidence: 99%

Clinical utility in infants with suspected monogenic conditions through next‐generation sequencing

Hong

Wang

Zhao

et al. 2019

Molec Gen & Gen Med

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Background Rare diseases are complex disorders with huge variability in clinical manifestations. Decreasing cost of next‐generation sequencing (NGS) tests in recent years made it affordable. We witnessed the diagnostic yield and clinical use of different NGS strategies on a myriad of monogenic disorders in a pediatric setting. Methods Next‐generation sequencing tests are performed for 98 unrelated Chinese patients within their first year of life, who were admitted to Xin Hua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, during a 2‐year period. Results Clinical indications for NGS tests included a range of medical concerns. The mean age was 4.4 ± 4.2 months of age for infants undergoing targeting specific (known) disease‐causing genes (TRS) analysis, and 4.4 ± 4.3 months of age for whole‐exome sequencing (WES) (p > 0.05). A molecular diagnosis is done in 72 infants (73.47%), which finds a relatively high yield with phenotypes of metabolism/homeostasis abnormality (HP: 0001939) (odds ratio, 1.83; 95% CI, 0.56–6.04; p = 0.32) and a significantly low yield with atypical symptoms (without a definite HPO term) (odds ratio, 0.08; 95% CI, 0.01–0.73; p = 0.03). TRS analysis provides molecular yields higher than WES (p = 0.01). Ninety‐eight different mutations are discovered in 72 patients. Twenty‐seven of them have not been reported previously. Nearly half (43.06%, 31/72) of the patients are found to carry 11 common disorders, mostly being inborn errors of metabolism (IEM) and neurogenetic disorders and all of them are observed through TRS analysis. Eight positive cases are identified through WES, and all of them are sporadic, of highly variable phenotypes and severity. There are 26 patients with negative findings in this study. Conclusion This study provides evidence that NGS can yield high success rates in a tertiary pediatric setting, but suggests that the scope of known Mendelian conditions may be considerably broader than currently recognized.

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Undiagnosed Diseases: Italy-US Collaboration and International Efforts to Tackle Rare and Common Diseases Lacking a Diagnosis

Cited by 25 publications

References 4 publications

SpainUDP: The Spanish Undiagnosed Rare Diseases Program

SpainUDP: The Spanish Undiagnosed Rare Diseases Program

A compilation of national plans, policies and government actions for rare diseases in 23 countries

Clinical utility in infants with suspected monogenic conditions through next‐generation sequencing

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