PREcision Diagnostics in Rare genetIC Diseases and Tumors - Long Read Sequencing

Condition(s) studied

Investigational drug(s) / intervention(s)

DNA/RNA sequencing and bioinformatic data analysis: DNA will be extracted from peripheral blood or from somatic tissues. In some cases a skin biopsy will be performed to obtain fibroblasts for further analysis (DNA/RNA extraction and preparation of cell culture for high-throughput genomic and epigenomic technique (Hi-C). LRS will be performed on extracted DNA using Oxford Nanopore Technology by two different approaches: * Target, in samples with monoallelic alterations in genes related to autosomal recessive disease; * Genomic in other cases. Sequencing data will be analyzed through a dedicated bioinformatics pipeline, to reconstruct the tridimensional structure of chromatin and the regions

Study summary

Using long-read sequencing (LRS) technology to achieve molecular diagnosis in patients with rare genetic diseases who have already been tested by state-of-the-art genetic analysis with ambiguous or negative results. This will lead to efficient and reliable identification and clinical interpretation of cryptic and complex structural genomic variants, which represent the central challenge for the coming decades in human genetics.

Eligibility

Primary outcome measure(s)

• The first aim of this study is to use LRS to reach a molecular diagnosis in patients with RGD that were already tested with state-of-the-art genetic analysis, with ambiguous or negative results. — 10 months
  In patients with RGD that were already tested with state-of-the-art genetic analysis, with ambiguous or negative results, will be use LRS to detect cryptic genomic variants that couldn't be detected with previous techniques. Clinical information of patients will be collected and integrated with genetic data.

Trial sites (1)

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