Diagnostic testing for neurogenetic disorders

28 June 2021

Molecular geneticist, Jo Martindale, answers In Touch’s questions about how the genetic testing regime works in New Zealand.

Firstly, perhaps you could broadly explain the difference between genetic testing and genome testing? 
Genetic testing refers to testing of a single gene or a group of genes associated with a specific condition. An example would be looking at the SMN1 gene in patients clinically suspected of having SMA, or perhaps a panel of genes associated with different types of SMA if the initial SMN1 gene test was not the answer.
In contrast, genomic testing doesn’t have a specific target - it is directed at all genes and would be likely to be used in cases where a patient has a number of features which collectively don’t correspond to a specific condition, or perhaps has had a number of genetic tests that haven’t provided an answer.

What muscular dystrophy conditions can people be tested for in New Zealand? 
• Duchenne and Becker muscular dystrophy.
• Myotonic dystrophy type 1.
• The most common forms of spinocerebellar ataxia (SCA1, 2, 3, 6 and 7).
• Fragile X-associated Tremor Ataxia (FXTAS).
• Charcot-Marie-Tooth type 1A / Hereditary Neuropathy with liability to Pressure Palsies, X-linked CMT.
• Spinal muscular atrophy (SMA).
• Spinobulbar muscular atrophy (SBMA) / Kennedy disease. Other tests can be arranged but are done outside New Zealand.

Are you often testing for a variety of symptoms/genes to get to a diagnosis?
For some conditions, yes. Anything that is very heterogeneous (i.e. a number of genes can cause the same or a similar condition) may well need further testing if the initial test is negative. An example would be inherited ataxias, where the commonest forms would be tested for first and then there would be reflex to a broader selection of genes if the initial test is negative.

How is it decided what will be tested for? 
The referring clinician generally specifies the condition that needs to be tested for and the genetics lab would then usually do any in-house test available for that condition. If further testing needs to be done other labs’ offerings will be examined and a decision will be made based on the most appropriate test. For non-genetics referrals, Genetic Health Service may be consulted about what is appropriate. There are lists available showing which genes have strong evidence for association with different conditions to help in the decision-making.

Where do people go to get the testing done? 
The blood test can be done anywhere that has a phlebotomy service. The sample will be forwarded on to the nearest genetics lab and processed from there. The results go back to the referring physician.

Must they have a referral from a specialist?
In general, yes. Most diagnostic referrals come through neurology (including paediatric neurology), paediatrics or Genetic Health Service NZ. Pre-symptomatic or prenatal testing can only be accepted via Genetic Health Service NZ.

Is testing free?
Obviously any lab test does have a cost attached to it. However, when testing deemed clinically necessary has been requested by an appropriate clinician, it is funded through the public health system so there is no cost to the patient.

What are the most common type of tests requested by clinicians/patients?
Diagnostic testing for neurogenetic disorders is usually requested by an appropriate specialist, e.g. a neurologist. Patients may wish to have carrier testing or pre-symptomatic testing but it’s important that the appropriate counselling is undertaken first.

We understand that some tests are sent offshore – why is this and how long does that take to get the results?  
Samples will be sent overseas when the testing isn’t available in New Zealand. The length of time to get the results varies by lab and the complexity of the test that has been requested, so can range from a few weeks to several months.

Where do the offshore tests go to? 
It depends on the condition. For example, facioscapulohumeral dystrophy testing is sent to Bristol in the UK, since they have specialist expertise in this condition. Otherwise, tests could go to Australian, European or North American laboratories.

Would that be for quite rare conditions? 
Again, it would depend on the complexity of the test required. Some conditions are individually rare but collectively, relatively common. A gene panel is generally the most cost-effective and quickest way to achieve a diagnosis for disorders that are heterogeneous. If you were looking for a condition that could be caused by hundreds of different genes, each of those genes may only contribute a tiny fraction of the overall frequency of the condition. In the “old days” it was common to do sequential gene testing. An example is HSP – the gene which contributes the most, the SPAST gene (SPG4), accounts for about 40 percent of autosomal dominant HSP. Before the onset of gene panel testing that single gene would have been tested first, probably followed by the ATL1 gene (SPG3A) which accounts for 10-15 percent of dominant HSP. Each of these gene tests would be very laborious and time-consuming and cost several hundred dollars so the cost would quickly mount up and getting the result could take quite a long time. It’s possible to get a gene panel test covering up to 25 genes for under $1000 now.

For further information see:
Genetic Health Service NZ 
Canterbury Health Laboratories
LabPlus Diagnostic Genetics 
Wellington Regional Genetics Laboratory 

Jo Martindale MSc, FRCPath is the Head of Molecular Section, Wellington Regional Genetics Laboratory and the current Chair of the NZ Branch of the Human Genetics Society of Australasia.


This article was originally published in the Winter 2021 edition of In Touch magazine. 

For more information please contact: 
Melanie Louden 
Communications and Marketing Advisor 
Muscular Dystrophy Association of New Zealand 
027 509 8774 
[email protected]