DNA Tests – South East Scotland Genetic Service

Samples for DNA extraction only

The DNA lab is happy to receive blood from any patient for DNA extraction for storage: DNA can be stored whether or not testing is available or considered appropriate at the time (see below). It is the responsibility of the referring clinician to ensure that appropriate consent has been obtained and documented.

Postnatal DNA tests

Only a restricted range of tests are available without prior discussion with Clinical Genetics:

Developmental Delay/ Fragile X syndrome
Angelman / Prader-Willi syndrome

Any paediatrician based in South-East Scotland can request tests for Angelman / Prader-Willi syndromes and testing for confirmed Developmental Delay , including Fragile X syndrome testing (see below).

Developmental delay

Diagnostic investigation of an abnormality in neurocognitive development is one of the most common reasons for referral to the genetic laboratory services. Almost all of these referrals come from paediatric services, in particular, community child health, paediatric neurology and general paediatrics.

Many different terms are used to describe this common clinical presentation including learning disability, mental handicap and global developmental delay.

We now offer a microarray test to investigate chromosomes for deletions and duplications in patients that fit our criteria (see Cytogenetic’s page). This test can detect the majority of known microdeletion and microduplication syndromes including;

1p36 deletion
2p16 microdeletion
3q29 microdeletion
9q22.3 microdeletion
15q24 deletion
17q21 microdeletion
22q13/ Phelan-McDermid
Cri du Chat, DiGeorge (22q11)
DiGeorge region 2 (10p15)
Langer-Giedion
Miller-Dieker
NF1 microdeletion
Prader Willi/ Angelman
MECP2 duplication
Rubinstein-Taybi
Smith-Magenis
Sotos
WAGR
Williams
Wolf-Hirschhorn

All requests for abnormal neurocognitive development testing should be sent to Cytogenetics for Microarray testing (samples will also be forwarded to Molecular department for Fragile X testing if appropriate).

If a specific syndrome is suspected this should be noted on the request form. We also request that some indication of whether the learning disability is mild, moderate or severe is provided if possible.

Referral to clinical genetics is recommended if:

there is a family history of learning disability or
craniofacial dysmorphism or
associated congenital malformation or
significant abnormality in prenatal or postnatal growth (overgrowth, failure to thrive, micro or macrocephaly etc)

suspected syndrome diagnosis that requires molecular analysis or
for estimation of recurrence risks

Triplet repeat disorders

Testing for a number of distinct conditions that have a common underlying mechanism of expansion of triplet repeats (Huntington disease, spinocerebellar ataxias, myotonic dystrophy) is available to regional neurologists.
Criteria for testing, using Huntington Disease as an example, can be found on the Testing symptomatic patients for Huntington Disease page.

Please note that referral to Clinical Genetics is required, prior to testing, in the case of a known family history of these diseases and is recommended in others.

Infantile Spinal Muscular Atrophy (SMA) and/or Myotonic Dystrophy testing

A request for urgent DNA testing for infantile SMA and/or myotonic dystrophy that is required to confirm a clinical diagnosis in a floppy baby can be submitted by any regional paediatrician. Other tests, e.g. for carrier status with a positive family history, should be discussed in advance with Clinical Genetics.

Heritable Bleeding, Platelet & Thrombotic Disorders

Samples are accepted from the Scottish Haemophilia Centres and associated clinics for a number of disorders associated with heritable coagulation and platelet disorders.
The laboratory is a member of the UK Haemophilia Centre Doctors Organisation (UKHCDO) Genetics Laboratory Network, which provides a national network of quality genetic diagnostic services for patients families with inherited bleeding and thrombotic disorders.
Samples should be accompanied by a Molecular Haematology request form and UKHCDO genetic testing consent form or a genetic lab request form, which contains the same record of discussion.

Genetic testing available includes:

Haemophilia A (F8)
Haemophilia B (F9)
von Willebrand disease (VWF)
Fibrinogen (FGA, FGB & FGG)
Deficiencies of coagulation factors II (F2), V (F5), VII (F7), X (F10), XI (F11), XIII (F13)
Rare causes of heritable predisposition to thrombophilia: protein S (PROS1), protein C (PROC) and antithrombin III (SERPINC1) Platelet disorders including Bernard Soulier Syndrome (GP1BA, GP1BB, GP9) and Glanzmann Thrombasthenia (ITGB3, ITGA2B)

Testing methodologies include sanger sequencing, next generation sequencing, MLPA dosage kits and inversion analysis, as appropriate. In addition, a Bleeding & Platelet gene panel provides testing for a range of coagulation related genetic disorders and is used for large genes and referrals with more than one candidate gene.

Other DNA tests

Clinical Genetics (0131 537 1116) should be consulted before requesting any test other than those noted in the previous section.

Other diagnostic laboratory tests

A number of other tests are available, either in our lab or

those of other members of the Scottish Molecular Genetics Consortium:

The Scottish Test Directory for Rare and Inherited Disease lists all available tests including referral criteria and relevant requesting specialties.

Other tests offered by UK labs participating in the National Genomic Test Directory

or from other European accredited diagnostic labs may also be available.

Research laboratory tests

There is currently no NHS funding for DNA testing performed outside of registered diagnostic labs. The DNA lab is happy to extract and store DNA from any sample received: Any further processing must be discussed with the Head of Lab who will seek the opinion of Clinical Genetics before sending a sample away.

Prenatal DNA testing

Rapid QF-PCR Trisomy Screen

The QF-PCR trisomy screen is the only prenatal DNA test directly available to regional clinicians and is undertaken in the Cytogenetics laboratory. A QF-PCR trisomy screen is available on solid tissue samples and is also undertaken by the Cytogenetics Laboratory.

Other prenatal tests

Prenatal testing for a number of other conditions is possible. Requests for all other tests are coordinated via Clinical Genetics: The ease of interpretation of genetic tests varies widely, as do the implications for individual(s) tested. In some cases, samples from the extended family need to be analysed to allow correct interpretation of results.

The workup required for individual tests and families varies considerably, so the lab may require some advance warning even after a test request has been approved. Specimens from additional family members are often required and must have been tested before receipt of foetal sample.

Even for previously tested couples, advance notice of specimen collection is essential to allow the lab time to plan for the urgent test and its disruption factor. Couples known to be at high risk from previous testing who are attending for subsequent pregnancies should be notified to the lab at first booking appointment.

When testing early in gestation is preferred, using CVB, please discuss in advance with the lab the amount of biopsy needed (range 2mg-20mg) which depends on the assays involved.