Targets of Newborn Screening
Targets of Newborn Screening
The NSO molecular laboratory provides molecular diagnostic testing for all diseases on Ontario’s newborn screening panel except for hemoglobinopathies (HBA and HBB testing is available at Hamilton Health Sciences Centre), cystic fibrosis (CFTR sequencing and deletion/duplication analysis is available at the Hospital for Sick Children; please note that we do offer a CFTR common mutation panel for carrier testing only - see below) and severe combined immune deficiencies (we only offer ADA and PNP testing; severe combined immune deficiency gene panels are available outside of Ontario with approval from the Ministry of Health). This testing is organized into panels, and all genes are also available as single gene tests. Beyond the diseases specifically targeted by newborn screening, some panels also include genes for related diseases.
We accept samples from patients of all ages and for multiple indications. Diagnostic testing can be requested for any individual who presents with symptoms of these disorders. Carrier testing can also be requested (including familial variant testing and full gene sequencing for reproductive partners); for further details regarding eligibility for carrier testing, please see our carrier testing policy. Prenatal diagnosis and maternal cell contamination studies are also offered (see FAQ for more details).
Testing methodologies
- Inborn errors of metabolism (IEM):
- NGS targeted panel for all genes
- qPCR common variant testing for CD320 (p.Glu88del) and CPT1A (p.Pro479Leu).
- MLPA deletion/duplication testing for PAH and ACADM and common variant testing (ACADM)
- Congenital adrenal hyperplasia:
- 21-Hydroxylase deficiency: Sanger sequencing, long-range PCR and MLPA
- "Other" panel: NGS targeted panel
- Cystic fibrosis:
- MassArray CFTR common mutation panel (for list of mutations, please see our molecular diagnostics gene list)
- Spinal muscular atrophy:
- ddPCR/MLPA
- Severe Combined Immune Deficiencies: testing for the ADA and PNP genes is available via NGS
Test limitations for next generation sequencing targeted panels
Not all exons are captured equally well, resulting in some regions that are consistently underrepresented (>99% of targeted regions will have >30X read depth for coding bases; >99.7% at >20X), with 20X coverage as our minimal quality standard for reporting. Sanger sequencing will be used to supplement NGS for targets with <20X read depth for any coding base, and/or for variant validation. Copy Number Variation (CNV) analysis is not fully validated. Our capture methodology along with NGS does not detect large deletions, insertions, chromosomal abnormalities or large rearrangements. We continue to refine our approaches to CNV analysis and updates will be posted here. Please feel free to contact us if you have questions about coverage for possible variants in any genes, generally or in the context of a specific patient.