[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100515839":3},{"organization":4,"armGroups":7,"interventions":23,"overallOfficials":30,"centralContacts":35,"locations":43,"responsibleParty":61,"collaborators":29,"id":63,"slug":64,"hasResults":65,"nctId":66,"briefTitle":67,"officialTitle":67,"acronym":68,"eligibilityCriteria":69,"healthyVolunteers":70,"sex":71,"minAge":29,"maxAge":29,"enrollmentInfo":72,"targetDuration":29,"studyType":75,"phases":76,"briefSummary":78,"conditions":79,"keywords":84,"overallStatus":46,"whyStopped":29,"lastUpdateSubmitDate":90,"lastUpdatePostDateStruct":91,"startDateStruct":94,"completionDateStruct":96,"leadSponsor":98,"locationsCount":99},{"fullName":5,"class":6},"Mario Negri Institute for Pharmacological Research","OTHER",[8,14,19],{"label":9,"type":10,"description":11,"interventionNames":12},"Healthy subjects","ACTIVE_COMPARATOR","Five healthy donors will be asked to participate in the study to set up the condition for isolation and culture of skin-derived fibroblasts and to establish the RNA-Seq conditions and profile.",[13],"Procedure: Skin biopsy",{"label":15,"type":16,"description":17,"interventionNames":18},"Validation cohort","EXPERIMENTAL","To develop a diagnostic pipeline for isolation and sequencing of mRNA from cultured skin fibroblasts, 10 adult patients with known genetic defects affecting RNA levels and\u002For splicing will be enrolled, as positive controls.",[13],{"label":20,"type":16,"description":21,"interventionNames":22},"Discovery cohort","The second group, the discovery cohort, will be composed of 30 undiagnosed symptomatic patients with clinical suspicion of a genetic disease (both children and adults with onset in infancy or early adulthood) referred to the Clinical Research Center for Rare Diseases \"Aldo e Cele Daccò\", and for which WES analyses did not reveal any causative genetic alteration. To this end, the investigators plan to recruit around 60 patients, their available parents and\u002For their available informative relatives who will undergo WES, if not previously done. On the basis of literature and their experience, the investigators expect that WES will be resolutive in 40-50% of cases. Consequently, investigators hypothesize to identify 30 patients with a negative WES who will enter the discovery RNA-Seq cohort.",[13],[24],{"type":25,"name":26,"description":27,"armGroupLabels":28,"otherNames":29},"PROCEDURE","Skin biopsy","A punch biopsy is a 15-minute low-risk procedure performed through a sterile circular blade (usually 3-4 mm) under local anesthesia. Briefly, the instrument is rotated down through the forearm epidermis and dermis perpendicular to its physiological lines of relaxation and into the subcutaneous fat, by producing a cylindrical core. Punch biopsy site can be closed with a single suture and generally produce only a minimal scar.",[20,9,15],null,[31],{"name":32,"affiliation":33,"role":34},"Marina Noris, PhD","Istituto Di Ricerche Farmacologiche Mario Negri","PRINCIPAL_INVESTIGATOR",[36,40],{"name":32,"role":37,"phone":38,"phoneExt":29,"email":39},"CONTACT","+3903545351","marina.noris@marionegri.it",{"name":41,"role":37,"phone":38,"phoneExt":29,"email":42},"Elena Bresin","elena.bresin@marionegri.it",[44],{"facility":45,"status":46,"city":47,"state":48,"zip":49,"country":50,"countryCode":51,"cosmosGeoPoint":52,"geoPoint":57,"contacts":58},"Centro di Ricerche Cliniche per le Malattie Rare \"Aldo e Cele Daccò\"","RECRUITING","Ranica","BG","24020","Italy","IT",{"type":53,"coordinates":54},"Point",[55,56],9.71335,45.72328,{"lat":56,"lon":55},[59],{"name":41,"role":37,"phone":60,"phoneExt":29,"email":42},"0039 035 45351",{"type":62,"investigatorFullName":29,"investigatorTitle":29,"investigatorAffiliation":29,"oldNameTitle":29,"oldOrganization":29},"SPONSOR","100515839","developing-a-pipeline-to-employ-rna-seq-as-a-complementary-diagnostic-tool-in-rare-diseases-100515839",false,"NCT05996731","Developing a Pipeline to Employ RNA-Seq as a Complementary Diagnostic Tool in Rare Diseases","ANTHEM","Healthy subjects.\n\nInclusion Criteria:\n\n* Male and female adults\n* Written informed consent\n\nExclusion Criteria:\n\n* Inability to understand the potential risk and benefits of the study\n* Legal incapacity\n\nValidation cohort.\n\nInclusion criteria:\n\n* Male and female adults\n* Genetic diseases affecting RNA levels (frameshifts, stop, large deletions, alteration of canonical splicing sites)\n* Written informed consent\n\nExclusion criteria:\n\n* Underage patients\n* Inability to understand the potential risk and benefits of the study\n* Legal incapacity\n\nDiscovery cohort.\n\nInclusion criteria:\n\n* Male and female patients (children and adults with onset in infancy or early adulthood) with rare genetic undiagnosed diseases\n* Patients with no strong candidates based on previous genetic analysis such as WES, but with clinically suspicion of a genetic rare disease\n* Written informed consent\n\nExclusion criteria:\n\n* Inability to understand the potential risk and benefits of the study\n* Legal incapacity",true,"ALL",{"count":73,"type":74},105,"ESTIMATED","INTERVENTIONAL",[77],"NA","This project aims to identify, through RNA-Seq technology, the genetic alterations underlying undiagnosed rare diseases in pediatric and adult patients with early onset and with negative WES.\n\n* Objective 1: Set up and validate techniques. Set-up and validation of the transcriptome analysis protocol in healthy subjects and in patients with known splicing alterations and\u002For altered RNA expression.\n* Objective 2: Diagnostic phase. Study of splicing alterations and RNA levels in cultured fibroblasts obtained from skin biopsies of patients with rare genetic diseases and negative exome.\n\nExploratory goals\n\n* Compare the RNA expression profile obtained from skin biopsy-derived fibroblasts with the RNA expression profile from blood. The most relevant results will be validated in qRT-PCR.\n* To analyze the transcriptional and protein profile heterogeneity in skin-derived fibroblasts in enrolled subjects.\n\nTo explore the effects of genetic (from WES) and transcriptional (from RNA-seq) alterations in participants' plasma and serum.\n\nHealthy controls Five healthy subjects will be recruited from the staff of the Mario Negri Institute for Pharmacological Research. The coded samples will be used to set up the method of isolation and culture of skin fibroblasts and RNA-Seq.\n\nValidation group For the set-up and validation of the skin fibroblast isolation and RNA-Seq procedure, ten adult patients with known diagnosis and with alterations in RNA levels and\u002For splicing will be recruited as positive controls.\n\nPatients who meet the requirements described above will be contacted by the doctors of the Daccò Center for an interview explaining the project. Those who agree to participate in the study will be asked to sign the informed consent before proceeding with the experimental part.\n\n\"Discovery\u002FExploration\" group The exploration cohort will be composed of 30 symptomatic undiagnosed patients with suspected genetic disease (children and adults with infantile onset) belonging to the Clinical Center of the Mario Negri Institute for Pharmacological Research and for whom WES investigations did not reveal causative genetic alterations.",[80,81,82,83],"Atypical Hemolytic Uremic Syndrome","Membranoproliferative Glomerulonephritis","Autosomal Dominant Polycystic Kidney","Healthy",[85,86,87,88,89],"Undiagnosed genetic rare diseases","Whole-exome sequencing","RNA-Sequencing","Molecular diagnosis","Skin-derived fibroblasts","2026-03-19",{"date":92,"type":93},"2026-03-23","ACTUAL",{"date":95,"type":93},"2024-02-21",{"date":97,"type":74},"2026-06",{"name":5,"class":6},1]