What Causes Polydactyly? The Inheritance of Polydactyly and the Gene that Causes It

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What Causes Polydactyly?

Being polydactyly is not uncommon, as it’s reported to occur in 1 in every 500 live births. The extra finger (s) or toe (s) tend to be poorly developed and are sometimes just tissue without any bone being present. Although, some extra digits can be functional. Errors occur during foetal development and they are caused by one of several mutations on a gene that is located on the short arm of chromosome 7.

What Gene Causes Polydactyly?

One gene that can cause polydactyly is GLI3, and it is one of a number of genes that are known to be involved in the patterning of tissues and organs during development of the embryo. It does this by helping to control whether specific genes are turned on or off. That is because GLI3 is a transcriptional repressor, which means that it codes for a protein (in fact a DNA-binding protein) that regulates the expression of one or several genes by decreasing the rate of transcription.

Mutations of the GLI3 gene during development are known to cause/contribute to two types of polydactyly.

Isolated post-axial polydactyly - which is more common amongst African-Americans and is where the extra digits are located on the small digit side (little finger, little toe) of the hand or foot. The mutations are located in the 7p13 region of the gene. Two other locations on this gene have also been identified as housing mutations that cause polydactyly.

Pre-axial polydactyly - is more common amongst Asian populations and is where the extra digits are located on the large digit side (thumb/big toe) of the hand or foot. The genetics here are not as clearly defined as post-axial polydactyly, but it is more likely to occur with other congenital abnormalities such as the fusion of skin between some fingers and toes. Other conditions that have polydactyly as a feature include Smith-Lemli-Opitz syndrome and Down syndrome. Mutations in GLI3 appear to be a contributory cause of some cases of pre-axial polydactyly.

There are several different types of post-axial and pre-axial polydactyly and their classification depends on their location, severity, and functionality. Other genes may also cause polydactyly, including LMBR1.

A fuller understanding of how genetic mutations cause polydactyly will be achieved when scientists have worked out all the genes that GLI3 interacts with during development, and the nature of these interactions.

The Inheritance of Polydactyly

Polydactyly follows an autosomal dominant pattern of inheritance which means that a) it is not sex-linked, so that boys and girls may be equally affected and b) a child who has a polydactyl parent has a 50% chance of being polydactyl too.