Currently, the majority of patients with DSD do not have a molecular diagnosis. Although high throughput sequencing is having an impact on the clinical diagnosis of DSD the accurate interpretation genomic datasets of the identification of new gene mutations causing DSD is challenging. This is due to emerging evidence that DSD may be caused by mutations in many different genes and the prevalence of mutations in a single gene may be very low. As larger number of DSD patients are subject to genomic sequencing, there is an increasing concern about the ability to robustly establish causality for novel candidates. To build evidence to support causality, there is a need to share genomic data between groups. This is important because the misidentification of DSD genes will have severe consequences for the patients and their families as well as in the development of targeted gene panels for DSD diagnosis. Within the EU COST Action DSDnet, we established a secure platform for sharing genomic data between interested groups. SDgeneMatch allows researchers to deposit lists of genes that carry one or more mutations in at least one patient sample and have these lists cross-checked with the lists uploaded by collaborators, without revealing the whole list to these collaborators. To prevent revealing any patient-specific information, only the bare minimum of information is collected by the system, which is a list of mutated genes that may be potential candidates for the phenotype. This means that it is not necessary to specify in which sample a gene was mutated or specify the type of mutation. A match occurs when two users of the system are found with a mutation in the same gene. Matches are reported to the two researchers that supplied the relevant gene identifier, and the matching gene symbol is disclosed to them. Reporting of matches is done behind the password-protected environment of SDgeneMatch, ensuring only the users that originally uploaded the match will be able to learn the gene name of the match. Other users will be made aware that a match has occurred, but will not learn the gene name. SDgeneMatch is specific for DSD and the DSD research community is actively encouraged to submit data into the system. This should accelerate gene/mutation discovery in the field and it will lead to a more accurate ascertainment of the genes that are involved in DSD leading to a robust molecular diagnosis for DSD.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology