Diagnostic Use
Guideline for Referral
Microarray (molecular karyotype) analysis is undertaken on fetal and extra-fetal tissue samples where a chromosome abnormality is suspected.
G-banded karyotype analysis (chromosomes) is not routinely performed, as microarray replaces conventional karyotype analysis for this referral type.
It is essential to provide the following information when referring a sample:
- Gestational age
- Suspected disorder/diagnosis
- List of all symptoms/phenotypes directly relevant to the suspected diagnosis
- Explanation of family history (if present)
- NHI or lab number of previously tested family members (if applicable)
Samples prior to 20 weeks gestation:
- History of recurrent miscarriage (3rd consecutive miscarriage)
- Abnormalities detected on ultrasound, or at post-mortem, congenital abnormalities, intra-uterine growth restriction, fetal loss following abnormal maternal serum screen test.
- Known familial chromosomal rearrangement,
- Confirmation of other prenatal testing (e.g. non-invasive prenatal testing).
Samples 20 weeks gestation or later:
- Intra-uterine death (IUD), stillbirth, neonatal death (NND), Fet death in utero (FDIU).
- Abnormalities detected on ultrasound, or at post-mortem, congenital abnormalities, intra-uterine growth restriction, fetal loss following an abnormal maternal serum screen test.
- Known familial rearrangement.
- Confirmation of other prenatal testing (e.g. non-invasive prenatal testing).
Samples received with no/insufficient clinical information or clinical details not meeting the referral criteria will not be fully processed for microarray analysis.
Referring clinicians will be informed, in writing, that these samples will be stored for 6 months and analysis can be undertaken if appropriate clinical information is provided.
Samples will be disposed of in accordance with laboratory policy after 6 months from date of receipt.
Test Method
Illumina Infinium Global Screening Array-24 v3.0 with analysis performed in NxClinical 6.2.
Experimental details and limitations:
1. Microarray analysis performed using the Illumina Infinium Global Screening Array-24 v3.0 with analysis performed in NxClinical 6.2. This platform offers a minimum detection limit of 15 kb with a requirement of at least 15 probes for copy-number detection. Losses smaller than 1 Mb or gains smaller than 2 Mb will not be reported unless associated with a gene/region of known pathogenicity.
2. Regions of homozygosity (ROH) are not reported, however the data is retained by the laboratory. Detection threshold for long contiguous stretches of homozygosity (LCSH) / regions of homozygosity (ROH) is set at 5 Mb.
3. Where a normal female karyotype is reported, using tissue from products of conception, there is a slight chance that it has been obtained from DNA of maternal origin.
4. Microarray analysis will not detect balanced alterations, point mutations, imbalances of regions not represented on the microarray and may not detect low level mosaicism. Microarray may not detect all forms of tetraploidy, and may not distinguish triploidy from triandric tetraploidy.
5. Genome build is GRCh38 (hg38). Nomenclature is according to ISCN (2020).
6. Classification of copy number variants: copy number variants (CNVs) are classified in accordance with the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) Technical Standards 2019, into the following five classes: Benign; Likely Benign; Uncertain Significance (3a, 3b, 3c), Likely Pathogenic, Pathogenic.
Benign, likely benign, and VUS 3c copy number variants are NOT reported. VUS 3b may be reported following consultation with Clinical Genetics.
Heterozygous carrier status for recessive conditions is not routinely reported. Data on all CNVs are retained by the laboratory should it be required.
Duplications of the SHOX region are not routinely reported.
Male Y chromosome changes are not reported except in cases of suspected aneuploidy. Supporting documentation regarding the interpretation of variants is available from the Diagnostic Genetics Laboratory; please contact us on DGen@adhb.govt.nz .
The classification of copy number variants represents the best interpretation of the data at the time of reporting. We recommend that the status of copy number variants is reviewed by the referring clinician to ensure their continuing validity.
7. The results and interpretations assume that the samples received by the laboratory are correctly identified and that family relationships and clinical diagnosis are as stated.