SpainUDP

SpainUDP integrates Human Phenotype Ontology (HPO)–annotated phenotypic data with whole-exome sequencing (WES) analysis to accelerate diagnosis of rare undiagnosed diseases and enable international genomic data sharing.

Key Features:

• Phenotype standardization: Phenotypic data are documented using the Human Phenotype Ontology (HPO) for standardized and detailed clinical characterization.
• Sequencing technology: Genetic data are obtained using whole-exome sequencing (WES).
• Bioinformatics processing: WES data are processed through a standard bioinformatics pipeline.
• Variant validation: Candidate variants are validated by Sanger sequencing.
• International data sharing: Participation in RD-Connect, Solve RD, the Undiagnosed Diseases Network International (UDNI), and MatchMaker Exchange (MME) enables cross-project data sharing and variant matching.
• Cohort outcomes: From late 2015 to early 2018 SpainUDP accepted 147 cases (110 active), completed phenotypic and genotypic characterization for 30 cases yielding 20 diagnoses (67%), had 21 cases awaiting Sanger validation, 25 cases with ongoing WES, and 34 cases undergoing deeper phenotypic characterization.

Scientific Applications:

• Rare disease diagnosis: Integration of HPO-based phenotyping and WES to provide molecular diagnoses for patients undiagnosed after extensive evaluation.
• Variant matching and gene discovery: Cross-platform data sharing through MME, RD-Connect, Solve RD, and UDNI to facilitate variant matching and novel gene discovery.
• Phenotype–genotype correlation: Combined phenotypic and genotypic characterization supports case-series analyses and research into rare disease mechanisms.

Methodology:

Phenotypic annotation using Human Phenotype Ontology (HPO); whole-exome sequencing (WES) data processed via a standard bioinformatics pipeline; candidate variant validation by Sanger sequencing; data sharing and matchmaking through RD-Connect, Solve RD, UDNI, and MatchMaker Exchange (MME).