Whole Genome Sequencing Panel – Osteogenesis imperfecta

Diagnostic Use

Health NZ and Illumina (a global genomics technology supplier) have embarked on a two-year clinical pilot to trial whole genome sequencing (WGS) and comprehensive genomic profiling (CGP) of cancer in New Zealand’s public health system. The project will build genomic infrastructure, reduce reliance on overseas testing, and evaluate the clinical and economic impacts of NZ based testing.

Clinical testing will commence in late Sept 2026. Canterbury Health Laboratories (CHL) will offer whole genome sequencing (WGS) as a diagnostic tool for individuals and families thought to be affected by a rare genetic disease. The testing range offered includes family duos, trios and quads, as well as selected singleton panels on a genome backbone (see Test Manager entry for Whole Genome Sequencing Panels). Singleton WGS (Mendeliome analysis) will not be offered as part of this diagnostic service.

Osteogenesis imperfecta (OI) or “brittle bone disease” is a genetically and phenotypically heterogeneous heritable skeletal disorder with an incidence of 1:15,000–20,000 live births (PMID 39127989). OI is primarily characterised by bone fragility and deformity, growth deficiency and highly variable secondary connective tissue findings, including blue sclerae, dentinogenesis imperfecta (DI), cardiovascular and respiratory defects, hearing loss, and joint hypermobility. OI inheritance patterns include autosomal dominant and recessive, as well as an X-linked recessive form. The majority of individuals with OI (80–85% in Western countries; about 60% in countries with a high incidence of consanguinity) are caused by structural or quantitative defects in collagen type I, due to pathogenic variants in the COL1A1 and COL1A2 genes. OI is a collagen-related disorder, with rarer types of OI caused by defects in genes whose protein products interact with collagen, as well as those that affect primarily bone mineralisation and osteoblast differentiation.

Referrals for testing will be accepted only if endorsed by an appropriately qualified medical specialist such as a Clinical Geneticist, Metabolic Physician, Paediatrician, or Endocrinologist, either directly or via a multidisciplinary team meeting.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Laboratory Handling

Phlebotomy

Take a separate sample for this testing - no shared tubes please.

Constituent Tests

• Genomic DNA Extraction

Synonyms

Genome
WGS
Osteogenesis imperfecta
OI

Turnaround Time

8 weeks

Specimen Type

• Whole Blood
• DNA extract

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

Minimum Sample Volume (ml)

0.5

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Pre-testing Requirements

Urgent referrals for this testing can be accommodated with reporting times of 3-4 weeks from receipt of all samples. Please notify us of urgent samples via email to CT-genelab.test@TeWhatuOra.govt.nz or using the contact link below.

Additional Specimen Information

This genetic test needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport at ambient temperature).

An aliquot of DNA extracted by another accredited diagnostic laboratory is also an acceptable sample type. DNA extracts should be at least 20uL of DNA at a concentration no less than 20ng/uL. Please contact the laboratory to discuss specific requirements if the available DNA does not meet these standards.

We would also appreciate it if referral laboratories could provide 280/230 and 260/230 ratios where possible.

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Test Method

Where relevant for prenatal samples, maternal cell contamination of the sample is examined by comparison of fetal and maternal genotypes at 19 highly polymorphic markers using the Elucigene QST*R plus v2 kit.

Genome library preparation is performed using PCR free tagmentation prep on a NovaSeq X Series 25B flow cell and sequenced on an Illumina NovaSeq X instrument. FASTQ output files are uploaded to the Emedgene platform, where alignment to the GRCh38/hg38 human reference genome and variant calling are performed using the Illumina DRAGEN pipeline.

Analysis is conducted using a validated in-house SOP (CHL Exome_Genome analysis v2) on Emedgene software, which filters variants based on population frequency, coding impact, inheritance patterns, presence within an OMIM gene, evidence of pathogenicity, and phenotype-genotype correlation. The test targets all coding exons and intron–exon boundaries within the selected panel (All genes) with a primary focus on genes known to be associated with Mendelian disorders.

Analysis is primarily focused on established disease genes previously associated with genetic disorders. Variants are assessed under relevant inheritance models, including potential de novo variants, autosomal dominant (with possible reduced penetrance), autosomal recessive, and X-linked patterns. Prioritisation is guided by the potential phenotypic relevance to the clinical information provided. Classification of variants follows current CHL laboratory policy, based on the ACGS Best Practice Guidelines (Ellard et al., 2020) and ClinGen gene-specific modifications where applicable (https://clinicalgenome.org/curation-activities/variantpathogenicity/documents/).

Where relevant, allele frequency data in New Zealand Māori populations is incorporated using the He Kākano / Aotearoa Māori Variome Resource for Clinical Diagnostic Purposes. Reporting uses HGNC gene symbols and HGVScompliant variant nomenclature.

Contact Canterbury Health Laboratories on +64 3 364 0484 or email LabInfo@cdhb.health.nz

Laboratories may prefer to submit DNA for testing. Please provide a minimum of 20 micrograms of DNA at 20 nanograms / microlitre.

Contact Information

Enquiry Form