Naked Science Forum
Life Sciences => Physiology & Medicine => Topic started by: dkerridge on 14/02/2003 21:19:48
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Motor Neurone Disease (MND) has been fairly prominent in the press recently with Diane Pretty's right to die court case and the more recent case in Switzerland.
Does anyone know of any current research into inherited MND?
My father, pateranl aunt and paternal grandmother all died of MND at a young age, 58, 37 & 44 respectively. Before my dad died a blood sample was taken and is currently stored at Addenbrookes. A blood sample was also taken from my aunt who died in the 1960's and I think this is still stored somewhere.
No mutations were detected in the SOD1 gene in my dads blood. Apparently mutations in the SOD1 gene are only found in 20% of all families with inherited MND.
Any info or advice would be gratefully received. I'm not particularly scientific or medical so no words longer than 20 syllables please !!!
Thanks for your interest
Duncan
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Duncan - I'll look into this too.
Best wishes
Chris
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Dear Duncan
thanks for your question; sorry it has taken a little time to provide some useful information, but with sensitive situations like that in your family we wanted to be sure that we had not missed anything.
We pursued several avenues and spoke with a number of neurologists and pathologists. Their suggestions are summarised below :
"The information on the MNDA website (see below) answers the question pretty much. There's SOD-1 and recently ALSIN (aka ALS-2)which has been found in a Tunisian and a Kuwaiti family, but the phenotype is atypical - slowly progressive, mostly lower motor neurone signs. I don't think that anyone is doing clinical testing for this gene yet - and it would seem very unlikely that this would be the cause in your family. Other loci have been identified but the causative genes have not yet been determined.
It's very difficult and frustrating for people with familial ALS."
"Your figure of 20% of cases having identifiable SOD1 mutations is about right. They raised a couple of points, the first being whether the diagnosis of ALS was definite, as HSP (hereditary spastic paraplegia) and adult onset hexosaminidase A deficiency can mimic familial ALS. Other dominant loci associated with ALS are ALS with frontotemporal dementia on chromosome 9q22 and ALS4 on 9q34, so far no genes indentified.
The other point is that over 90 mutations in all 5 exons of SOD1 have been identified and it may be that your questioner's SOD1 may have been only partially screened (exon 1 A4V mutations account for about 50% of US familial ALS).
Recessive ALS (which doesn't fit with your questioner's family history) aka ALS2 and ALS5 which have been identified in Tunisian pedigrees have loci at 2q33 and 15q15-q22 but both forms present much earlier (between 3 and 23 years).
X-linked dominant forms (which may be relevant in your questioner- but not to him himself) have been described but there is no known gene and no known locus.
Essentially with regard to SOD1 testing, a negative result does not rule out FALS due to low mutation detection rates.
I guess most importantly is that presymptomatic testing for SOD1 mutations is pretty controversial due to incomplete penetrance, inability to predict age of onset and lack of preventive measures. A lot of neurologists and geneticists will utilise a Huntington-style protocol of counselling before testing."
Duncan - you are probably already acquainted with the Motor Neurone Disease Association, but here is the URL for their site which provides an extremely readable overview of the field :
http://www.mndassociation.org/full-site/what/index.htm
The material that the guys are quoting above regarding new kindreds and genes related to ALS are also summarised on the site here :
http://www.mndassociation.org/full-site/research/gene.htm
Hope this helps,
TNS