Rare Diseases Service
The Rare Diseases Service performs and reports on a range of tests from simple PCR based assays to detect one specific mutation or a small set of mutations, right up to genome-scale sequencing.
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– Constitutional Genomics
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– Link to NHSE test directory- Rare and inherited diseases
Constitutional Genomics
Constitutional Genomics Enquiries
Y&NE GLH
Clinical Advice
Sample Types
Techniques Available
Rare Diseases Service
The Rare Diseases Service performs and reports on a range of tests from targeted testing, multiple gene panel screened through to whole genome sequencing (WGS)
National Genomics Test Directory
The National genomic test directory for rare and inherited disease details the tests available for rare and inherited disease
Tests are ordered by referencing the clinical indication as defined in the Directory. Each clinical indication has an “R” number and to ensure timely processing this code will need to be included when you are requesting the test. It is also important to include further pertinent clinical information in order to support the laboratory analysis.
The eligibility criteria document, available here, supplements the National genomic test directory by setting out which patients should be considered for testing under that indication, and the requesting specialties is a list of the clinical specialties who would be expected to request the test.
Testing location
The Newcastle Genetics Laboratory, through the North East and Yorkshire Genomics Laboratory Hub (NE&Y GLH) https://ney-genomics.org.uk/ partnership, provides core and specialised genomics services. Where specialised testing is provided by an external GLH the Newcastle Laboratory will arrange export of sample.
Whole Genome Sequencing
Many indications have now moved to Whole Genome Sequencing (WGS) in line with the National Genomic Test Directory https://www.england.nhs.uk/publication/national-genomic-test-directories/.
Supporting information for the WGS service & the links to the forms, eligibility & sample requirements can be found here.
The full list of available WGS test services is found here.
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Constitutional Enquires
Email: nuth.constitutional.genomics@nhs.net
Address:
Newcastle Genetics Laboratory
Central Parkway
Newcastle upon Tyne
NE1 3BZ
Head of Department:
Dr David Bourn PhD FRCPath, Clinical Scientist – Genetics david.bourn@nhs.net
Rare Disease Genomics Lead Scientist:
Dr Ciaron McAnulty PhD FRCPath, Clinical Scientist – Genetics ciaron.mcanulty@nhs.net
Cancer Genomics Lead Scientist:
Gavin Cuthbert FRCPath, Clinical Scientist – Genetics gavin.cuthbert@nhs.net
Microarray Service/ Constitutional Genomics Service Lead:
Shaun Haigh, Clinical Scientist – Genetics – shaun.haigh@nhs.net
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Y&NE GLH
Newcastle Genetics Laboratory is part of the Yorkshire and North East Genomic Laboratory Hub (Y&N GLH). For information of the NHS England Genomic Laboratory Hubs – see https://www.england.nhs.uk/genomics/genomic-laboratory-hubs/.
Genomic testing is delivered in accordance with the NHS England National Genomic Test Directory – https://www.england.nhs.uk/publication/national-genomic-test-directories/
Y&NE GLH Operational Director:
Dr Angie Silmon PhD angela.silmon@nhs.net
Y&NE GLH Laboratory Services Director:
Kath Smith FRCPath, Clinical Scientist – Genetics – kath.smith4@nhs.net
Y&NE GLH Lead Scientist for Rare Diseases:
Ruth Charlton FRCPath, Clinical Scientist – Genetics Ruth.Charlton1@nhs.net
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Sample Types
Blood Samples
G-Banding and FISH requires a fresh blood sample in a Lithium- or Sodium-Heparin tube, which needs to be received within 72hrs of sampling. G-Banding is the preferred technique for trisomy detection (such as trisomy 21 in Down syndrome) and sex chromosome aneuploidy (such as 45,X Turner syndrome).
SNP array analysis requires DNA, which is usually extracted from a fresh blood sample (sent in an EDTA tube). Blood samples need to be received within 72hrs of sampling. Please contact the Laboratory if you require different samples tested (such as buccal swabs).
Prenatal Samples
Amnio
Chorionic Villi
Pregnancy Loss Samples
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Constitutional Techniques Available
Karyotyping (G-Banding)
SNP Array Analysis
FISH
QF-PCR
Whole Genome Sequencing (WGS)
Next Generation Sequencing (NGS)
Prenatal Sample Techniques
Pregnancy Loss Sample Techniques
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G-banded metaphase chromosome analysis is predominantly used to identify genome-wide balanced structural abnormalities such as translocations and inversions.
-Banding requires a fresh blood sample in a Lithium- or Sodium-Heparin tube, which needs to be received within 72hrs of sampling. G-Banding is the preferred technique for trisomy detection (such as trisomy 21 in Down syndrome) and sex chromosome aneuploidy (such as 45,X Turner syndrome).
Chromosome studies can usually be completed within 28 days (10 days in cases with urgent clinical need).
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Single Nucleotide Polymorphism array analysis throughout the Y&NE GLH uses the Illumina CytoSNP-850K v1.2 BeadChip platform. SNP array analysis can identify genome wide copy number changes (gains and losses) as well as absence of heterozygosity (AOH), which is seen in some forms of Uni-Parental Disomy (UPD). The average backbone resolution is approximately 50kb and the average targeted gene resolution is approximately 10kb.
SNP array analysis requires DNA, which is usually extracted from a fresh blood sample (sent in an EDTA tube). Blood samples need to be received within 72hrs of sampling. Please contact the Laboratory if you require different samples tested (such as buccal swabs).
SNP array analysis is the preferred front line test for developmental delay, learning difficulties, multiple congenital abnormalities, behavioural disorders, dysmorphism and other developmental disorders.
Analysis and interpretation is based on the referral reasons given. SNP arrays will NOT detect balanced rearrangements or point mutations and have limited sensitivity for the detection of mosaicism. SNP arrays cannot detect certain forms of UPD without parental samples and do not give locations or orientations of imbalances. Consanguinity and copy number variants considered to be of no clinical significance will not be reported. Carrier status for recessive disorders may not be reported. It is our policy to review results in the light of newly published literature and further testing and reporting will be carried out where necessary.
SNP array analysis can usually be completed within 28 days (14 days in cases with urgent clinical need).
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Fluorescence in situ hybridisation (FISH) for constitutional cases is rarely carried out and is usually only used to supplement family studies or sometimes to confirm SNP array findings which are below the resolution of G-banding.
FISH, like G-Banding, requires a fresh blood sample in a Lithium- or Sodium-Heparin tube, which needs to be received within 72hrs of sampling.
FISH is carried out using commercially available probes (such as sub-telomeric kits).
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QF-PCR (Quantitative Fluorescence-Polymerase Chain Reaction)
QF-PCR is a rapid molecular test to identify the common aneuploidies, specifically chromosomes 13, 18, 21 and the sex chromosomes.
QF-PCR testing can be carried out on blood from new-born babies, on prenatal samples and on pregnancy loss samples.
Babies and children with referral reasons indicative of aneuploidy or sex chromosome disorders will be processed by QF-PCR in the first instance. If a normal result is obtained from QF-PCR, the sample will also be processed by SNP array.
QF-PCR will not detect balanced structural rearrangements and may not detect mosaicism.
Rarely, testing of prenatal samples may be uninformative or fail to give a result either due to maternal cell contamination or other factors. Maternal and paternal blood samples may be requested to help interpret results.
For same day processing, prenatal samples should arrive at the laboratory before 13:00 hrs. We aim to report all prenatal and urgent postnatal QF-PCR results within 2 working days.
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Next Generation Sequencing (NGS)
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