A new PSP genetic risk factor screener

Genetic screening is emerging as a routine and necessary step in clinical research in the neurodegenerative diseases. If you’re looking for the cause of a family cluster, for example, you have to rule out the genetic variants already known to be associated with that disease. If you’re working up a geographical cluster of PSP, as my colleagues in France and I are, you have to look for a genetic founder effect before embarking on a difficult search for environmental causes, and the place to start is with gene variants already known to increase disease risk.
Pathological overlap among the various neurodegenerative diseases is another major current theme. For example, LRRK2 mutations can cause any of a number of pathologies, including PSP, and the tau H1 haplotype is associated with PSP, CBD and PD. It would therefore be convenient to have a single genetic screening device would allow different labs studying different diseases to compare or merge results.
Such a gizmo is now here. It’s a superset of Illumina’s Infinium HumanExome BeadChip called NeuroX. It tests for not only the standard 242,901 gene variants usable in studying any condition but also an additional 24,706 variants focusing on Alzheimer’s, Parkinson’s, MSA, ALS, FTD, multiple sclerosis, Charcot-Marie-Tooth disease, myasthenia gravis — and PSP. The chip is designed to allow easy substitution of subsequent versions of both the basic Illumina chip and easy addition of new neurological variants.
The first author of the report in Neurobiology of Aging is Mike Nalls and the senior author is Andrew Singleton, both of the NIH. The genetic variants included in the chip were derived from multiple genome-wide analyses over the past 20 years. Disclosure: I’m listed way down on the list of “authors” because I was a leader of “GenePD,” one of the consortia whose findings were used in constructing the new chip.  But I have no financial interest in the invention.
At a cost of $57 per sample plus the cost of the basic machine and technician time, you won’t have to be a drug company or the NIH to afford a statistically meaningful series; genetics core labs will be able to offer this as a routine procedure.


8 thoughts on “A new PSP genetic risk factor screener

    • There is no genetic test for PSP to date. There is a form of the MAPT gene (the gene that encodes the tau protein) that occurs in about 95% of people with PSP and about 65% of the rest of the population. That’s a pretty big genetic effect, but it’s not large enough to use as a diagnostic test. There are a handful of other genetic variants that are present in slightly different proportions in people with and without PSP, but they’re also not useful – or available – as diagnostic tests. Over the next few months, a new genetic study of PSP using a new technology, whole-exome sequencing, will be completed. I hope that it will point toward a genetic diagnostic test, but I’m not very hopeful. Even if we had a genetic test for PSP, we still wouldn’t know how to determine the age at which symptoms would begin. Onset age is probably controlled by different genes that would have to await still further studies.

      • I’m not sure what you mean by “sps parkinson,” but genetic testing for PSP is not really available, as I mention in my comment above. That comment describes the H1 haplotype in the tau gene, which has insufficient predictive power. There is another exception, but it applies only in families with multiple members with PSP. One or more people with PSP in such families can have their tau (MAPT) gene sequenced in search of a “point mutation,” which means the alteration of a single nucleotide. About a dozen such mutations have been identified as causes of familial PSP-like illnesses. A clinical geneticist or genetics counselor would then have to give an opinion as to whether the variant found is more likely the cause of the illness as opposed to an “innocent” random variant. Then, healthy people in the family can be tested for that mutation. But most such “at-risk” individuals prefer not to know if they’re carrying a disease-causing mutation.

  1. Thank you for posting this. My father,too, died from PSP. It took over 3 years to get the right diagnosis, not that it would have mattered. Please keep researching!

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