PRPH

The PRPH gene provides instructions for making a protein called peripherin. Several molecules of peripherin bind together to form intermediate filaments, which provide support and strength to cells. Intermediate filaments also assist in positioning the nucleus and other specialized structures within the cell. In addition, these filaments appear to relay signals from the cell surface to the nucleus. These signals play a role in regulating cell development and growth.

Peripherin is found in nerve cells of the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and sound (sensory cells). The exact function of peripherin is unclear. Additional peripherin is made when nerves are injured, which suggests that it plays a role in the repair of nerve cells. In particular, peripherin may be involved in the regrowth of axons, the specialized extensions of nerve cells that are essential for the transmission of nerve impulses.

amyotrophic lateral sclerosis - increased risk from variations of the PRPH gene

Researchers have identified two mutations in the PRPH gene that increase the risk of developing amyotrophic lateral sclerosis. These genetic changes are very uncommon. One mutation, written as 228delC, deletes a single DNA building block (base pair) from the PRPH gene. This mutation is predicted to lead to an abnormally small peripherin protein, which appears to impair the assembly of peripherin into intermediate filaments.

The other PRPH mutation changes one of the protein building blocks (amino acids) used to make peripherin. Specifically, the amino acid aspartic acid is replaced with the amino acid tyrosine at protein position 141 (written as Asp141Tyr or D141Y). This change probably affects the 3-dimensional shape of peripherin and leads to clumps (aggregates) of this protein within nerve cells.

It is unclear how PRPH mutations increase the risk of developing amyotrophic lateral sclerosis. Aggregates of peripherin and disturbed intermediate filaments likely disrupt normal nerve functions, leading to the decline and death of motor neurons. Motor neurons are specialized nerve cells in the brain and spinal cord that control muscle movement. The death of motor neurons is a characteristic feature of amyotrophic lateral sclerosis.