Postnatal Array CGH
Array CGH is a technique which screens the whole genome to detect copy number changes (unbalanced gains/duplications and losses/deletions of genetic material) which may be contributing to a child’s phenotype. In addition, SNP arrays can detect lack of heterozygosity, which in certain chromosomal regions (such as Prader-Willi syndrome) can also be pathogenic.
Change to testing
From the 7th January 2019 the platform the Leeds Genetics Laboratory uses to perform microarray testing will switch from an oligo array platform to a SNP (single nucleotide polymorphism) array platform. This technology offers greater sensitivity, higher resolution, and can detect large regions of homozygosity, such as may be observed in uniparental disomy. This is therefore expected to be of benefit to the diagnostic pathway.
This change will not affect sample requirements or referral pathways and will not be expected to have a detrimental impact on turnaround times. The wet laboratory work will be undertaken by the Newcastle Genetics Laboratory with the analysis, reporting and issuing of results all being performed by the Leeds Genetics Laboratory.
Users will during this transition receive both oligo and SNP reports, depending on the technology used, until the backlog of samples processed by oligo array has been reported. The reports will stay in the current format with minor changes.
Array testing is offered as a first line service for paediatric referrals with:
- Unexplained learning difficulties / developmental delay / behavioural problems (including autism and referrals for the fragile X phenotype).
- Dysmorphism / multiple congenital abnormalities suggestive of a chromosome abnormality.
Professional judgement is used to determine which patients are tested, in line with current lab policy.
Please note: All patients who are eligible for array CGH need to have had this test completed before a referral to Clinical Genetics can be accepted.
The laboratory will require a minimum of 1ml peripheral blood in an EDTA tube (purple top) with a Cytogenetics and DNA joint referral card which you can download from here. Please complete with comprehensive clinical details.
If an EDTA blood sample is not received for a patient an array will not be performed.
The laboratory turnaround times are taken from the ACGS (Association for Clinical Genetic Science) professional best practice guidelines and are as follows:
Proband (no follow up studies required):
95% within 4 weeks from receipt of a suitable DNA sample.
Parental blood samples requested after detection of imbalance in proband:
95% within 4 weeks from receipt of suitable parental blood samples and follow-up test material (e.g. FISH probes).
Samples from neonates are prioritised as urgent and the laboratory endeavours to obtain a result within 14 days.
Limits to Array CGH
- Array CGH will not detect all genetic abnormalities
- Array CGH cannot detect balanced chromosome rearrangements such as reciprocal translocations and inversions. Karyotyping will be carried out for patients suspected of these abnormalities.
- Array CGH cannot detect low level mosaicism (< 30% mixture of abnormal and normal cells)
- Anomalies may occur which cannot always be recognised or properly interpreted.
- Array CGH cannot detect mutations. Array analysis can detect small genomic imbalances which may disrupt genes and give a similar phenotype to a mutation but it is not sensitive enough to detect mutations within genes. Requests for specific mutation testing can be made to the laboratory (refer to molecular genetics section).
Alternative testing for samples suboptimal for array CGH
A technique, referred to as CNVseq (Copy Number Variant detection by Sequencing), was introduced into our laboratory in January 2014 to complement array CGH testing. The method uses a Next Generation Sequencing approach to look for copy number variation in the genome in a similar way to array CGH. The technique is used for samples which are considered to be suboptimal for array CGH due to poor quality/low amount of DNA input. These samples are tested by CNVseq instead of array CGH, with the same guidelines for analysis and reporting being applied. Due to the nature of the test, the resolution obtained per case will vary; this will be stated in the report. Please note that the test is currently performed only once every month. As a result, the turnaround times may be slightly higher compared to array CGH.
Fragile X testing
Referrals for patients with a genetically confirmed family history of Fragile X (clinical information of affected family member must be provided) will be tested on request.
Since 1st August 2015, all other samples have array testing performed as a first line test as it has a higher detection rate of causative abnormalities than the Fragile X test. It cannot, however, detect the Fragile X mutation. If following a normal array result Fragile X testing is still required, a newly completed referral form must be sent to the laboratory in order for testing to be initiated.
As array CGH is a whole genome screen there may be occasional unexpected incidental findings which are medically important but unrelated to the specific reasons for referral. It is important to explain to the parents that the test is a very detailed look at the whole of the genome and occasionally unexpected incidental findings are detected. In the event of the laboratory detecting a clinically relevant incidental finding, the laboratory will contact the referring clinician before issuing the report.
Clinical advice is available from the Department of Clinical Genetics, Chapel Allerton Hospital, Leeds. The team are happy to receive referral letters for patients that have had abnormal array CGH results and/or where there are clinical implications for other family members.