(mentions CMT) Identification Of Gene Linked To Rare Form Of Progressive Hearing

[Guest guest]

Identification Of Gene Linked To Rare Form Of Progressive Hearing Loss In Males

http://www.medicalnewstoday.com/articles/174470.php

A gene associated with a rare form of progressive deafness in males has been

identified by an international team of researchers funded by the National

Institute on Deafness and Other Communication Disorders. The gene, PRPS1,

appears to be crucial in inner ear development and maintenance. The findings are

published in the Dec. 17 early online issue of the American Journal of Human

Genetics.

" This discovery offers exciting therapeutic implications, " said F. Battey,

Jr., M.D., Ph.D., director of the NIDCD. " Not only does it give scientists a way

to develop a targeted treatment for hearing loss in boys with this disorder, it

may also open doors to the treatment of other types of deafness, including some

forms of acquired hearing loss. "

The gene is associated with DFN2, a progressive form of deafness that primarily

affects males. Boys with DFN2 begin to lose their hearing in both ears roughly

between the ages of 5 and 15, and over the course of several decades will

experience hearing loss that can range from severe to profound. Their mothers,

who carry the defective PRPS1 gene, may experience hearing loss as well, but

much later in life and in a milder form. Families with DFN2 have been identified

in the United States, Great Britain, and China.

The NIDCD-funded researchers led by Xue Zhong Liu, M.D., Ph.D., of the

University of Miami School of Medicine, discovered that the PRPS1 gene

encodes the enzyme phosphoribosylpyrophosphate (PRPP) synthetase 1, which

produces and regulates PRPP (phospho-ribosylpyrophosphate), and appears to play

a key role in inner ear development and maintenance. The four mutations

identified in the PRPS1 gene cause a decrease in the production of the PRPP

synthetase 1 protein that results in defects in sensory cells (called hair

cells) in the inner ear, and eventually leads to progressive deafness.

" PRPS1 is an interesting example of a human disease gene in which gain of

function or loss of function mutations cause several different and distinct

hereditary disorders, " says Dr. Liu. " Our findings emphasize the body's need for

tight regulation of PRPP synthetase 1 since a drop in activity can lead to

deafness. " Other mutations in the PRPS1 gene have been linked to

neurodegenerative disorders such as Arts syndrome and a form of Charcot-Marie

Tooth disease, both of which feature deafness in the constellation of symptoms.

Knowing that a reduction in the amount of PRPP synthetase 1 is what causes

deafness in DFN2, Liu and his colleagues are now exploring potential enzyme

replacement therapies to either restore hearing or prevent further hearing loss

in boys with DFN2. They believe that since the PRPS1 mutations can be used as a

genetic marker for DFN2, in the future at-risk boys could be tested at birth and

immediately put on enzyme replacement therapy to reduce or prevent the hearing

loss that would ordinarily come later in life.

In addition, the knowledge that scientists gather about the mechanisms of PRPS1

potentially could be used to develop treatments to combat acquired hearing loss,

such as the hearing loss caused by drugs that are used in some chemotherapy

regimens and treatments for HIV/AIDS. These are powerful and helpful

medications, but they have the unfortunate side effect of damaging, even

killing, hair cells in the inner ear. The results from this study open the

possibility for improving these life-saving treatments by eliminating or

reducing the disabling side effect of hearing loss.

In addition to NIDCD support, the following institutions collaborated in this

study: Chinese PLA General Hospital, Beijing; University of Science and

Technology of China, Hefei; Chinese Academy of Sciences, Hefei; Guizhou

Provincial People's Hospital, GuiYang, China; UCL Institute of Child Health,

London; Shanghai Institutes for Biological Sciences, Chinese Academy of

Sciences, and Shanghai Second Medical University, Shanghai; Department of

Genetics, Harvard Medical School, Boston; Massachusetts Eye and Ear Infirmary,

Boston; and Medical Institute, Boston.