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Archive for March, 2012


28 Mar, 12 | by Steve Vucic, Web Editor

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disorder of motor neurons in the cortex, brainstem and spinal cord, for which there is no cure.  The pathophysiological mechanisms underlying ALS remain to be fully elucidated, although approximately 10% of cases were previously regarded as familial.  Mutations in the superoxide dismuate-1 gene (SOD-1) were first reported in 1993, accounting for ~20% of all familial ALS cases.  Recently, two independent research groups have made a stunning discovery, whereby large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 gene located on chromosome 9p21 was reported to account for between 23.5-46% of familial and 21.1% of sporadic forms of ALS (DeJesus-Hernandez et al. 2011; Renton et al. 2011).   In addition to the typical ALS phenotype, this genetic mutation was also associated with frontotemporal dementia, suggesting a potential link between these two disorders.  The mechanisms by which this genetic mutation results in the AL/FTD phenotype remains to be fully elucidated, although a loss-of-function and RNA-mediated gain-of-function mechanisms have been proposed.  Further research is required to clarify the precise mechanisms mediating the neurodegenerative processes in ALS.  Resolution of such issues could be of profound therapeutic significance.

In this issue of JNNP, Dr Bryan Traynor, one of the senior authors on the original manuscript in Neuron, provides historical commentary on the discovery of this very important gene.  In addition, Khan and colleagues further expand the phenotype associated with this very important mutation by reporting a behavioural variant from of frontotemporal dementia (FTD).   This underscores the importance of this mutation in development of neurodegeneration and appears to be a game changer for the diagnosis of both ALS and FTD, having significant implications in the counselling of the so called “sporadic ALS” patients and FTD.


Traynor, B. J. Road to the chromosome 9p-linked ALS/FTD locus. Journal of Neurology, Neurosurgery & Psychiatry. 2012; 83: 356-357.

Khan, B. K., J. S. Yokoyama, L. T. Takada, et al. Atypical, slowly progressive behavioural variant frontotemporal dementia associated with C9ORF72 hexanucleotide expansion. Journal of Neurology, Neurosurgery & Psychiatry. 2012; 83: 358-364.

DeJesus-Hernandez, M., Ian R. Mackenzie, et al. (2011). “Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS.” Neuron 72: 245-256.

Renton, Alan E., E. Majounie, et al. (2011). “A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD.” Neuron 72: 257-268.

Who’s in Control Here?

15 Mar, 12 | by Clare Caldwell, Web Editor

According to a recently released study in Current Directions in Psychological Science, the key to self-control is practice. As in, the more you practice self-control, the more inclined you are to engage it when you need it most.

Take Wednesday night for example, when two excellent hours were spent at a concert, leaping around to seminal 1980s band New Order. Amongst the 5,000 or so revellers there were plentiful elbows to the ribs, hair flicked in faces and sprays of beer that were all happily endured in the name of good spirits. In any other circumstance these encroachments on the person would never be tolerated. However, the concert continued unabated without a visit from the riot police.

Nonetheless, my companion, who shall remain nameless but carries the XY chromosome, took a somewhat different approach to the evening. Whenever a flailing limb made contact or a stream of ale breached the meniscus of a fellow rocker’s plastic cup and became airborne in his direction, he would repay the action in kind…and with interest. The recipient of this harangue would stare wide-eyed at the angry man and wonder: why all the negative energy?

One’s tiny mind begins to tick over in these situations and draw tenuous links. And, in deference to New Order and its predecessor Joy Division, the title of the latter’s most intriguing song came to mind: She’s Lost Control. Why is it that one person can control their emotions when another can’t?

Back at the concert, the old grey matter was working overtime and came up with a theory. Where the psychological scientists of the aforementioned study had tortured their subjects by denying them chocolate biscuits or forcing them to hold a nasty King Pigeon pose (some breed of contortive yoga move), my XY friend had merely had “a hard day at work”. A nine-hour conga-line of whining clients and incompetents had slowly sapped his reserves of self-control and here was his chance to let loose.

Miraculously, two hours passed and no actual violence was perpetrated on another individual. However, a quick exit from the venue was followed by what turned out to be a 90-minute queue to leave the carpark. Again, good spirits reigned. Fellow carparkers tooted their horns in the style of New Order and generally made good of a tedious situation.

XY held his own for about 45 minutes…and then lost it. Alighting from the car and confirming that he was merely popping out to get a snack from the nearby convenience store, he returned 10 minutes later out of breath and electric. On enquiring, it turns out that he was probably lucky to have all limbs remaining. Allegedly, on finding a carpark attendant (a very large gentleman from the island of Tonga) behind glass on the lower level, he had engaged in some unsavoury chat and found that the attendant, too, had had a “hard day” and was happy to let XY know about it in a physical fashion. Evidently the flight/fight response had kicked in.

On the drive home, one was reminded of the lyrics of a tune pilfered from Tennessee Ernie Ford by the smooth old crooner, Tom Jones, called Sixteen Tons. “If you see me coming, better step aside. A lot of men didn’t, and a lot of men died.”

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