Its g-g-g-genetic

Pardon the title, but in somewhat shocking news (to me, anyways), it turns out stuttering is genetic. A study released today in the New England Journal of Medicine has identified mutations in two genes - GNPTAB and GNPT - that seem to cause stuttering. These mutations seem to be found in stutterers around the world, although the initial mutations were identified in a Pakistani family.

The real odd thing though is what these genes do - they're involved in sending proteins to lysosomes; our cells version of a garbage bin. Lysosomes are nasty places, where parts of our cells go to die - they're acidic, full of oxidents, and full of enzymes whose sole job is to destroy anything that fall into their maw.

Genetic diseases involving lysosomes are somewhat common, and while the exact symptoms vary depending on the gene(s) which are mutated, they all have a common thread - neurological problems. In fact, most of these disorders have profound - often lethal - effects on a patients neurology. So in some ways the link between stuttering and lysosomes makes sense - lysosomal mutations often have neurological outcomes. But the mildness, and limited affected area (speach, not much else) in this case is very, very odd.

So what exactly does GNPTAB and GNPT do? Turns out both are pieces of a large complex whose job is to tag proteins that need to be sent to lysosomes. This tag is a sugar (GlcNAc), and acts as a sorting signal that tells our body "this protein should go to a lysosome". Proteins tagged in this way are generally not being sent to lysosomes for degradation, but rather are the active components of lysosomes. So mutations in these genes should make for less active lysosomes, which in turn may lead to the buildup of damaged cell components in affected individuals.

How and why these mutations lead to stuttering remains a mystery. In fact, other mutations in GNPTAB are known to cause two severe disorders called "mucolipidosis types II and III"; disorders which cause sever cardiac, skeletal and eye issues. The fact that these mutations seem to selectively affect one region of the brain (presumably the speech centre) is particularity hard to explain, given the diverse effects of other mutations in the same gene.

Whether or not this discovery does anything to help stutterers is an open question - although it does get overbearing teachers and parents off the hook.

Kang, C., Riazuddin, S., Mundorff, J., Krasnewich, D., Friedman, P., Mullikin, J., & Drayna, D. (2010). Mutations in the Lysosomal Enzyme-Targeting Pathway and Persistent Stuttering New England Journal of Medicine DOI: 10.1056/NEJMoa0902630