Diagnosis; Mutation Confirmation

Establish or confirm diagnosis

Guidance for management

Predictive risk information for patient and/or family members

Reproductive decision-making

Mainly cases fulfilling Schwannomatosis clinical diagnsotic criteria where it is needed a genetic confirmation (complete study) or in cases where the analysis is needed to detect the presence of a previously identified mutation in a family (direct study).

DNA is extracted from a patient's sample. An NGS library is prepared and enriched by capture in solution using our custom hereditary cancer sub-exome target panel (ICO-IMPPC_HC_Panel_V2.0), which include the whole coding regions of NF2 (LRG_511), SMARCB1 (LGR_520) and LZTR1 (NG_034193.1) genes among others. Enriched library is sequenced in a … DNA is extracted from a patient's sample. An NGS library is prepared and enriched by capture in solution using our custom hereditary cancer sub-exome target panel (ICO-IMPPC_HC_Panel_V2.0), which include the whole coding regions of NF2 (LRG_511), SMARCB1 (LGR_520) and LZTR1 (NG_034193.1) genes among others. Enriched library is sequenced in a Illumina platform and data is bioinformatically analyzed for a primary QC. A dedicated bioinformatic pipeline analysis and a further manual inspection of NF1 and SPRED1 is performed to detect possible damaging variants, which are validated by Sanger sequencing. Regions of NF1 and SPRED1 covered by less than 30 reads per base are also analyzed by Sanger sequencing in case that no mutations were detected. The presence of partial or total NF1 gene deletions or duplications are analyzed using the MLPA (Multiplex Ligation-dependent Probe Amplification) technique. We also perform haplotype analysis of the NF1 region in patients and families when indicated. In suspected cases of mosaicism, the analysis was performed from two different tumor samples. Once detected the mutation, it will be confirmed by PCR and sequencing of exon DNA level involved in the other tumor sample. View more

Mutation is detected DNA level by NGS and validated by an independent technique (Sanger). Splicing mutations that are not previously described are also validated at RNA levels. Studies from patients with mosaicism two independent affected tissues from the same patient are analyzed to detect both first and second hits.

Tests performed
Entire test performed in-house

95% (n=20)

Deep intronic mutations, copy number alterations and gross rearrangements, mosaicism, RASopathies overlaping clinical manifestations

Is proficiency testing performed for this test? Help
No

Software used to interpret novel variations Help
Polyphen, SIFT, PROVEAN, Condel, HSF, NNSplice, SpliceAIDs,