Bulletin No. 4 – September 2005

FINDING AND DEFINING YOUR GENE MUTATION

Testing Cost and Availability

The HSP Research Foundation has heard from many members of the very high prices of HSP gene testing overseas (it can not be done in Australia yet).  The high cost to members has been limiting its adoption.  The HSP Research Foundation investigated the issue and used our new collective negotiating capability to get a better deal, ie. less than half former costs. 

The news was promulgated to Clinical Geneticists by Assoc. Prof. Martin Delatycki.  There are about 50 Clinical Geneticists in Australia attached to the major hospitals, all of whom now recognize the increased affordability of gene tests for HSP sufferers.  Consequently we wrote this Bulletin for members to explain the application, the benefits and the support for those who adopt gene testing.

We all carry about 35,000 genes (and increasing as science continues searching).  About twenty of these, when mutated/varied, can cause one of the different forms of HSP.  All HSP is caused by a gene mutation and half of the most common, “pure uncomplicated,” form of HSP is caused by only 2 genes – SPG4 and SPG3A.  The Neurologist can diagnose HSP with a quite high accuracy and determine whether it is the complicated or uncomplicated form.  But as far as the causal gene variation/mutation is concerned, the specialist can only give indications of what the gene might be.  In contrast, gene testing is definitive and accurate.

The results of genetic tests can do much to mitigate the impact of HSP at the family level for now and in the future.  The following outlines what can be done within the limits of current technology.  Genetic testing is also now much more affordable.

The cost to an HSPer of genetic testing is now less than half that it was a year ago.  A complete sequencing of the gene nominated by a Clinical Geneticist and/or Neurologist is carried out to find and describe the gene mutation causing HSP in a family.  This test result will apply equally to all family members showing the disease.  Other family members showing no signs of the disease are then able to screen for the presence of the mutation now defined whenever they wish.
 
As an example, the most common gene in the most common form of HSP (pure, uncomplicated) is SPG4 and, if the patient fits in to this pure category, the doctor would request full sequencing (to find and describe the mutation causing the disorder) of that gene in your sample of blood or DNA.  The probability of it being SPG4 is 40% but if it is negative, the next most common gene is SPG3A with a probability of 10%.  Therefore a second test may be necessary at the price provided and even then a result may not be found.  The cost of the SPG4 test is now down to $1,450 and SPG3A test is $1,610.  Family members can subsequently be tested for this already sequenced mutation for only $250 per test.  These prices have been negotiated with GENDIA of Belgium by the Hereditary Spastic Paraplegia Research Foundation.

The good news is that the costs are under half what they were a year ago and only one family member needs this full sequence because that will be the abnormal gene that pertains to the family.  The costs will often be shared across the family who can all benefit because the family sequence allows other family members (even those not born yet) to benefit from the $250 screen.  There are no extra medical charges associated with the process as a clinical genetics service is provided at Australia’s major hospitals by the State.  A normal blood sample is taken and most clinical genetics services will extract DNA and send that to GENDIA for analysis by GENDIA.  It is more costly to ship blood but GENDIA will accept it.
 

What are the benefits of Gene Testing?

*  It provides information for individuals so they can make life plans in the context of the new knowledge.  With children, this predictive testing is not permitted unless they show signs of having the disease because the person must be old enough to deal with the implications of a result.
 
*  Stopping the continuing inheritance of HSP in the family is possible with this genetic knowledge.  Knowledge of the mutation causing the disorder allows couples to choose to enter an IVF programme including pre-implantation genetic diagnosis, ie. implanting only embryos without the mutation, after embryos have been screened by gene testing.  Approvals would have to be gained for inclusion of HSP in IVF programmes but the above is being done successfully with other conditions.

*  Pre-natal testing would also be available once HSP approvals have been gained.

*  The peak onset age for HSP is in the twenties (ie. child bearing age) and it would be wise to determine the presence or absence of the gene mutation earlier rather than later because it can be passed on irrespective of the manifestation of the disease in the parent.

*  Any gene related therapy for the disease that may arise out of research will require knowledge of the causal mutation which can only be obtained by gene testing.  While gene therapy is many years away, the information will be just as relevant.

*  Your basic right to know is being exercised.

A referral by your Neurologist to the Clinical Geneticist (there are about 50 attached to Australia’s major hospitals and some private Labs with Clinical Geneticists) would start the genetic testing process and provide the geneticist with useful information.  Clinical Geneticists are also doctors and a referral is not necessary.

Following the visit, a well established protocol is followed.  This includes the important role of genetic counselling which involves a genetic counsellor gathering and recording genetic information and family relationships on your family tree and offering guidance to deal with new information when it becomes available.  This information is maintained by the gene counsellor for the family and privacy laws are observed even within the family.  The Clinical Genetics service apart from the cost of the genetic test is a service provided by the State in most cases.
 
It would be nice to complete this picture for members with news of a cure for existing HSP sufferers but more affordable gene testing is a significant move forward.

FOOTNOTE FROM THE PRESIDENT

The HSP Research Foundation policy is to encourage one member per household to join.  There is variation in practice and I ask if you would disseminate the information to each adult within the wider family via a copy of the Bulletin or at least ensure adults in the family are fully informed.

The contents of this Bulletin provide information that may assist individuals and families to make choices and it is not intended to give advice.  A clinical genetics service is available from major hospitals and I believe would welcome your contact should you decide to explore the matters further. 

Robin Bligh
President