Additional evaluation of selected gene from CarrierTest panel for matching

Additional testing for hidden carriage of key mutations in selected recessive genes that may affect the health status of carriers and their offspring. The matching uses the evaluation of data from the already performed CarrierTest NGS testing intended for donors. When to use this test: We use it to match the donor with the partner who carries the mutation in the selected gene to determine the suitability of using this donor and eliminate any reproductive risk.

Additional analysis and evaluation of selected genes and key mutations for matching is performed by an expert from archived data.

The results are obtained by massively parallel sequencing on the Illumina platform using the CarrierTest panel. The obtained data are further analysed according to our own bioinformatic evaluation, which includes alignment to the GRCh38 genome reference sequence, variant calling, annotation with the current version of Ensembl and filtering of target variants according to the current version of the panel. Each of the above steps is complemented by quality control. Complementary methods are used for the internal control of sample identification and confirmation of key or problematic variants: fragmentation analysis (SOP-MGL-004), MLPA (SOP-MGL-020), Sanger sequencing (SOP-MGL-030), PCR-hybridization strip assay (SOP-MGL-031). 

Note: 
CarrierTest is a screening method for the detection of selected pathogenic variants of class 4/5 genes tested (see the PDF files below for current list of tested variants and diseases). The pathogenicity assessment corresponds to current available clinical and scientific information and may be refined/modified in the future. The technical parameters of the method used do not guarantee 100% coverage of all targeted regions of the genome. The analytical sensitivity of the assay may be reduced in regions homologous to pseudogeneous sequences (e.g. CYP21A2, GBA, CBS genes), in repetitive regions and regions with a high amount of GC bases. A negative result does not exclude the possibility of a de novo mutation in the offspring of the proband. Detection of germinal or somatic mosaicism is only possible to a limited extent by this method. We cannot exclude mutations in other (uncovered, unanalysed, or unassessed) genes and changes that cannot be detected under the current level of knowledge and technical possibilities. All preparation and processing of the examined sample material is based on the highest and current scientific and analytical standards. However, as with any other laboratory test, possible inaccuracy of the result cannot be ruled out for procedural reasons (e.g. error in sample collection, labelling and processing, or in data collection and interpretation). The mentioned residual risks of carriage and risks of birth of the affected offspring by the disease are an estimate based on available information on the frequency of the tested variants within the Czech population or Slavic ethnic group. Residual risks may vary if one or both partners are of a different ethnicity. This diagnostic method was developed and validated by GENNET s.r.o. and accredited by the Czech Accreditation Institute according to ČSN EN ISO 15189:2013.

Infertility, repeated spontaneous abortions or IVF failures, positive history of hereditary disease in one of the partners or in the family, consanguineous marriages