Predictive testing – a partner carries the gene mutation from CarrierTest (including compatibility of the couple)
Material:
Quick test description:
When to use this test: The partner is already a known carrier of the gene mutation detected in our laboratory by CarrierTest. Therefore, the patient is indicated to be tested for all mutations of the gene, which will also be performed by CarrierTest and the compatibility of both partners determined.
Test details:
Using the CarrierTest, the next-generation sequencing (NGS) method is used to test the carriage of gene mutations that may affect the health of carriers and their offspring (for an up-to-date list of tested diseases and analysed variants, see the PDF below or visit www.gennet.cz/carriertest). In male patients, the detection of AZF (azoospermia factors) microdeletion on the Y chromosome – AZFa, AZFb, AZFc and SRY loci – is included in the test, but this result is commented on in the report only in case of microdeletion.
The risks for the examined persons and their offspring (the degree of genetic compatibility of the couple) are assessed in three categories:
I. Carriage of gene mutations associated with severe recessive diseases. Both positive and negative results are reported for the CFTR, SMN1 and GJB2 genes. Only positive findings are reported for the other genes tested.
II. Mutation in the panel of genes of congenital predisposition to increased risk of blood clotting (thrombophilic profile).
III. Response to hormone therapy of infertility (polymorphism of FSH receptor gene).
Method used:
Results are obtained by massively parallel exome sequencing (WES, >40Mbp) on the Illumina NovaSeq Xplus platform using the current version of the CarrierTest virtual panel. The obtained data are analysed according to our own bioinformatic evaluation, which includes mapping 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 the current list of variants and diseases tested). The evaluation of pathogenicity of the variants detected corresponds to current available clinical and scientific information and may be refined or modified in the future according to newly available facts and findings. 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.
