Guest Blogger Danio:
I know, I know. Friday night isn’t exactly the best time to smack you with a big messy fistful of science, but PZ will be kicking us Minions out of the house early next week, so I have to stay on schedule with these Usher posts if I’m going to get through Part IV by the time he shows me the door.
In Part I, I introduced the hereditary disease known as Usher syndrome and went over a bit of the cell biology of auditory and visual sensory cells. In this post, I’ll discuss the molecules known to be affected in Usher patients, and begin to describe what is known about their function.
As mentioned previously, variations in the clinical presentation of Usher syndrome have resulted in the creation of three clinical subtypes. Type 1 is characterized by severe to profound congenital hearing loss, balance problems, and early onset vision loss, usually beginning before the patient’s 10th birthday. The type 2 hearing loss is also congenital, but tends to be less severe. The vision loss in type 2 usually begins to occur a bit later, in the early teen years, and these patients do not present with balance problems. All three categories of symptoms–vision, hearing, and balance, are progressive, commencing in childhood or adolescence rather than at birth, in Usher type 3 patients.
Despite these differences, the specific combination of deaf-blindness, plus or minus balance defects, led researchers to predict that multiple mutations in a single gene, or perhaps in two or three genes at the most, would turn out to be responsible for the symptoms observed in all Usher patients. The advent of genetic mapping led to surprising results in this regard. To date, at least 11 different genes have been implicated in the disease, nine of which have been molecularly identified thus far. More surprising still are the natures of the proteins encoded by the identified genes. In contrast to signaling or metabolic pathways, in which a genetic defect at any point in the regulatory chain of events will adversely affect the target and result in an abnormal phenotype, the Usher proteins do not act in stepwise fashion to regulate a cellular process. What they actually do is not entirely clear at this point, but the various proteins contain functional domains known to be important for scaffolding, cell adhesion and signaling, extracellular matrix formation, and motor activity.
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