Pleiotropy

In human genetics, pleiotropy (from the Greek pleion, "more", and tropos, "path") refers to the phenomenon that occurs when a gene (pleiotropic gene/polyphenic gene) influences several seemingly unrelated phenotypic traits (trait expression/phenotype) at the same time.

For example, the effects of cytokines on several different target cells/target tissues are also referred to as pleiotropic (Avogaro A et al. 2018).

A typical example of a pleiotropic gene is the gene for phenylketonuria. The main phenotype is developmental delay. However, the blockage of biochemical performance causes other trait changes: light-colored hair, skin problems, cramps, etc.

A mutation in a pleiotropic gene can cause effects on different organs. For example, a mutation in the patched gene in nevoid basal cell carcinoma syndrome leads to numerous changes such as jaw cysts, hypertelorism, dimples on the palms of the hands and soles of the feet, etc.

Another example of pleiotropy is phenylketonuria (PKU). This disease causes mental retardation and decreased pigmentation of hair and skin. It can be caused by a variety of mutations in a gene on chromosome 12 that codes for the enzyme phenylalanine hydroxylase.

Phenylalanine hydroxylase converts the amino acid phenylalanine to tyrosine. Unconverted phenylalanine accumulates in the bloodstream and can lead to concentrations that are toxic to the developing nervous system of newborns and young children. Since the body uses tyrosine to make melanin, failure to convert normal levels of phenylalanine to tyrosine can result in light hair and skin.

1. Avogaro A et al (2018) The pleiotropic cardiovascular effects of dipeptidyl peptidase-4 inhibitors. Br J Clin Pharmacol 84:1686-1695.https://www.ncbi.nlm.nih.gov/pubmed/29667232
2. Itin P (2018) Fundamentals of genetics. In: G Plewig G et al (ed.) Braun-Falco`s Dermatology, Venerology and Allergology. Springer Reference Medicine S 35-43