Cytogenomic Tests – South East Scotland Genetic Service

Microarrays

Tel: 0131 537 2998

POSTNATAL

Microarray testing requests are welcome from Clinical Genetics, Paediatrics or Psychiatrists for Adults with Learning Disability, only for patients with;

Congenital malformation/abnormalities
Dysmorphic features
Failure to thrive in babies
Confirmed diagnosis of intellectual disability or of autism spectrum disorder
Epilepsy

or with significant delay in one or more of the following developmental areas;

Gross motor
Vision and fine motor
Hearing, speech and language
Social, emotional and behavioural

For referrals with limited clinical details, blood samples in both lithium heparin and EDTA will be processed and stored and a Phenotype Information Form will be issued. This can be completed and returned if microarray testing is still considered appropriate and testing will be actioned upon receipt. Repeat samples will not be necessary.

PRENATAL

Solid Tissue samples where there is a fetal anomaly/parental chromosomal rearrangement/history of recurrent miscarriage (sample should be processed by Pathology first).
Characterisation of prenatal abnormalities (e.g abnormal ultrasound or increased risk from Serum Screen)

ACQUIRED

Characterisation of Tumour samples e.g 1p19q co-deletions, MYC amplifications, TP53 deletions etc

Specimen Requirements

Two specimen tubes are required; one a lithium Heparin specimen tube, the other an EDTA (KE) tube. Arrange for immediate transport to the Cytogenetics Laboratory. if this is not available, blood specimens should be refrigerated. (DO NOT FREEZE) Referring clinicians are requested to comply with NHS Lothian policy on Mandatory Data Sets: Failure to do so will result in delays in processing or rejection of the sample.

TARGETED XON LEVEL ARRAYS

High resolution XON array analysis is available for the following clinical situations (only where an appropriate MLPA test is not available);

Confirmatory testing of a CNV identified using another method such as CNVs detected through NGS, or analysis with a different array type/platform, where confirmation/refinement of gene involvement is required.

Identification of a ‘second hit’ where a single pathogenic sequence variant has been identified in an autosomal recessive gene, and the phenotype of the patient is a good fit for this gene.

The clinician has a strong clinical suspicion of a particular disorder which can be caused by variants in one or a small number of genes, ideally for which CNVs have been reported in the literature.

These cases should be discussed and agreed at the Scottish dysmorphology meeting before a request to the lab is made.

FISH (Fluorescent In Situ Hybridisation)

Tel: 0131 537 1940

STRUCTURAL ABNORMALITIES

Complex chromosome rearrangements and sub-microscopic rearrangements can be studied by molecular cytogenetic techniques using chromosome paints.

CANCER CYTOGENETICS

The same techniques used to study structural abnormalities and aneuploidy in constitutional samples can also be used to study cancer cells. There are specific probes available to detect gene fusions that have arisen as a result of the rearrangement of specific genetic material.

Gene fusions currently detectable by FISH include:

BCR/ABL in chronic myeloid leukaemia
PML/RARA in acute promyelocytic leukaemia
ETV6/RUNX1 in acute lymphoblastic leukaemia
t(14;18) in follicular lymphoma

View the Repertoire of tests

QF-PCR
(Quantitative Fluorescence Polymerase Chain Reaction)

Small sections of DNA from the sample are amplified, labelled with fluorescent tags and the amounts measured by electrophoresis.

QF-PCR is used to measure gene dosage. It can be used to test for aneuploidy of whole chromosomes.

For PRENATAL/TISSUE samples aneuploidy for chromosomes 13,18,21,X and Y are tested
For NEONATAL BLOOD: The laboratory offers a rapid aneuploidy test for Chromosome 21.

Male Factor Infertility Kit

Y chromosomal microdeletions are the second most common cause of male infertility after Klinefelter’s syndrome with deletion frequencies varying between 2 and 10% in azoospermic men, dependent on patient selection (Krausz et al., 2023). Clinically relevant deletions have been identified in three regions of the Y chromosome, AZFa, AZFb and AZFc.