The carrier screening test is the largest pan-ethnic screening panel available. This panel analyses genes for pathogenic mutations known to cause autosomal recessive and X-linked disorders.
Diseases targeted: >400 Autosomal Recessive and X-linked Inherited Disorders
Our technology establishes Beacon as the most intensive carrier screening with the highest accuracy available.
- Sequence variants and small insertions/deletions: unless otherwise specified, whole gene sequencing (coding regions and adjacent intronic/splice regions) is performed with >99% of bases covered by at least 20 independent sequence reads (“20x”). Additionally, intronic and promoter mutations specified in ClinVar and the Human Gene Mutation Database (HGMD) are targeted with >98% sensitivity.
- Fragile X: The trinucleotide repeat (CGG) expansion in the 5’ untranslated region of FMR1 is detected by repeat-primed PCR (rpPCR). Premutation carriers are sequenced by Sanger sequencing to detect AGG interruptions.
- Spinal Muscular Atrophy: copy number changes in the SMN1 Point mutations for spinal muscular atrophy are not detected due to high sequence homology. (May be need to RT-PCR, regards to genetic counsellor request)
- Congenital adrenal hyperplasia (CDH): 21‐Hydroxylase deficiency (21‐OHD) caused by the CYP21A2 gene mutations is the most common form of CDH. It is an autosomal recessive disorder that results in defective synthesis of cortisol and aldosterone.
- Pseudogenes: proprietary bioinformatics tools are employed to identify carrier mutations in disease genes (such as GBA for Gaucher disease and HBA1/HBA2 for alpha thalassemia) which have highly similar inactive counterparts.
- Deletion/duplications (del/dup) by CGH array (Regards to your specialist request)
Reporting options: Only variants classified as “Pathogenic” or “Likely Pathogenic” using the ACMG guidelines for sequence variant interpretation will be reported.
Detection rate: A broad range of laboratory and computational tools are employed to ensure the highest detection rate. The analytical detection rate for all genes is >98%.
*Male patients will not be screened for X-linked conditions (e.g., FMR1, etc.). If an X-linked condition is suspected in a male patient, please contact Bion Medical Genetics Laboratory or a genetics professional about diagnostic testing for that particular disorder.
Test Limitations:
All sequencing technologies have limitations. This analysis is performed by Next Generation Sequencing (NGS) and is designed to examine coding regions and splicing junctions. Although next generation sequencing technologies and our bioinformatics analysis significantly reduce the contribution of pseudogene sequences or other highly-homologous sequences, these may still occasionally interfere with the technical ability of the assay to identify pathogenic variant alleles in both sequencing and deletion/duplication analyses. Sanger sequencing is used to confirm variants with low quality scores and to meet coverage standards. If ordered, deletion/duplication analysis can identify alterations of genomic regions which include one whole gene (buccal swab specimens and whole blood specimens) and are two or more contiguous exons in size (whole blood specimens only); single exon deletions or duplications may occasionally be identified but are not routinely detected by this test. Identified putative deletions or duplications are confirmed by an orthogonal method (qPCR or MLPA). This assay will not detect certain types of genomic alterations which may cause disease such as, but not limited to, translocations or inversions, repeat expansions (eg. trinucleotides or hexanucleotides), alterations in most regulatory regions (promoter regions) or deep intronic regions (greater than 20bp from an exon). This assay is not designed or validated for the detection of somatic mosaicism or somatic mutations.