Diagnosis; Mutation Confirmation; Pre-symptomatic; Prognostic; Risk Assessment; Screening

Guidance for selecting a drug therapy and/or dose

For patients suspected to this particular and patients with a positive family history for this disease, gene sequence analysis is recommended as the first step in mutation identification.

DNA is extracted from the patient specimen, PCR amplification and sequence analysis of the entire coding region/ or indicated exons plus additional flanking intronic or other non-coding sequence. Sanger sequencing is carried out and the sequence is visualized on a capillary sequencer. Sequencing is performed separately in both the forward … DNA is extracted from the patient specimen, PCR amplification and sequence analysis of the entire coding region/ or indicated exons plus additional flanking intronic or other non-coding sequence. Sanger sequencing is carried out and the sequence is visualized on a capillary sequencer. Sequencing is performed separately in both the forward and reverse directions. View more

Confirmation of identified mutations is done in an independent experiment.

Tests performed
Entire test performed in-house

This test detects >99% of described mutations

All coding sequences, including the flanking intron sequences are analyzed using direct sequencing. With this method we can detect point mutations and small deletions or insertions. The presence of larger deletions or duplications are analyzed by MLPA. Mutations outside the analyzed regions will not be detected.

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
European Molecular Genetics Quality Network, EMQN

Description of PT method: Help
For Proficiency Testing, both external and internal, we have Sanger-sequenced extensive numbers of PCR fragments, and the error rate is less than 0.01% (99.99% accuracy). We also have performed MLPA of large numbers of samples with the maximal possible technical accuracy (>99.8%). Technical specificity for methods used in our laboratory … For Proficiency Testing, both external and internal, we have Sanger-sequenced extensive numbers of PCR fragments, and the error rate is less than 0.01% (99.99% accuracy). We also have performed MLPA of large numbers of samples with the maximal possible technical accuracy (>99.8%). Technical specificity for methods used in our laboratory is estimated >99.5% and technical sensitivity >99.5%. Mutation detection reproducibility for Sanger sequencing is near to 100%. View more

Software used to interpret novel variations Help
Alamut (Interactive Biosoftware), including AGVGD, PolyPhen-2, SIFT and MutationTaster for missense predictions and MAXEntScan, NNSPLICE, GeneSplicer and Human Splicing Finder for splice predictions

Laboratory's policy on reporting novel variations Help
Our laboratory reports class 3 (unknown pathogenicity), class 4 (likely pathogenic) and class 5 (certainly pathogenic) variants.