Genetics and Usher syndrome

The problems associated with Usher syndrome are caused by mutations, or changing of structure, of genes. Genes are essentially sets of information, inherited from your parents, which dictate the growth and development of every cell in your body.

An easy way of thinking about this is to think of a gene as being an instruction to the body. It tells a developing body how to build eyes, skin, a heart and so on. A mutation of a gene can then be thought of as being similar to a spelling mistake in the instruction which, in turn, means the instruction is not ready properly by the body which can then cause problems.

In this section we provide some information relating to the genetics of each of the Usher subtypes as well as explaining how Usher is inherited.

Usher type 1

Genetics

Currently, there are a total of 6 genes associated with Usher syndrome type 1. Each gene is associated with a particular Usher subtype. They are as follows:

  • USH1B: MYO7A gene
  • USH1C: USH1C gene
  • USH1D: CDH23 gene
  • USH1F: PCDH15 gene
  • USH1G: USH1G gene
  • USH1J: CIB2 gene

How common is Usher type 1?

In the UK, Usher type 1 appears to be the second most common Usher type. According to the National Collaborative Usher Study carried out in the UK in 2003, of the 188 participants, only 25% had a confirmed Usher type 1 diagnosis via genetic testing.

However in other countries, Usher type 1 is more common.

Unlike Usher type 2 and 3, it is unlikely that a child with Usher type 1 would be misdiagnosed as having a different kind of hearing loss after the age of 10; this is due to the symptoms of RP being exhibited before puberty i.e. nightblindness. 

Usher type 2

Genetics

Currently, there are a total of 3 genes associated with Usher syndrome type 2. Each gene is associated with a particular Usher subtype. They are as follows:

  • USH2A: USH2A gene
  • USH2C: ADGRV1 gene 
  • USH2D: WHRN gene

How common is Usher type 2?

In the case of Usher syndrome type 2, data demonstrates that in some geographical locations Usher type 2 is the most prevalent but in other geographic locations Usher type 1 is most prevalent.  

According to the National Collaborative Usher study, Usher type 2 appears to be the most common form of Usher syndrome in the UK.

The data for Usher type 2 may be underestimated as children may not be diagnosed or may be mis-diagnosed as having non-syndromic hearing loss, by which we mean that no association with other signs and symptoms such as impaired vision has been made. 

Usher type 3

Genetics

Currently, there are a total of 2 genes associated with Usher syndrome type 3. Each gene is associated with a particular Usher subtype. They are as follows:

  • USH3A: CLRN1 gene

  • USH3B: HARS gene

How common is Usher type 3?

Usher syndrome type 3 is thought to be the rarest form of Usher syndrome, responsible for 2% to 4% of all Usher syndrome cases. Similar to the other types of Usher syndrome, it is more common in some geographic areas than others. Usher syndrome type 3, despite being the rarest Usher type, appears to be responsible for a greater proportion of Usher syndrome patients in Finland and Sweden as well as within the population of Ashkenazi Jews; 13% and 9% respectively.  

How is Usher syndrome passed on?

Modes of inheritance is the term that describes the ways in which parents pass on specific genes to their children to produce specific characteristics. Examples include eye colour, height, facial features. 

Usher syndrome is inherited, which means that it is passed from parents to their children through changed or mutated genes. Usher is autosomal recessive. 

Autosomal means that both males and females can have the disorder and can pass along the disorder to a child.

Recessive means that a person must inherit a change in the same gene from each parent in order to have the disorder. If only one change is inherited, the child will be a carrier of Usher syndrome but will not develop the condition themselves.   

Carriers

A person with one changed gene does not have Usher syndrome, but can pass either a changed or an unchanged gene on to his or her child. They are said to be a carrier because they ‘carry’ the gene with a mutation, but show no symptoms of the disorder.

Usually, parents who have normal hearing and vision do not know that they are carriers of an Usher syndrome gene mutation. It is when an affected family member begins to exhibit the characteristics of Usher syndrome that the unaffected family members begin to question their own genetics. 

If a ‘carrier mother’ and a ‘carrier father’ who each carry one copy of the same mutated gene (i.e. carriers of Usher syndrome) decides to have a child together then with each birth there is a: 

  • One in four chance of having a child with Usher syndrome.
  • Two in four chance of having a child who is a carrier but does not have Usher syndrome.
  • One in four chance of having a child who neither has Usher syndrome nor is a carrier.

This image is taken from the National Instiute of Health (NIH, 2008). It illustrates the inheritance pattern that occurs in autosomal recessive conditions 

The above image is taken from the National Institute of Health (NIH, 2008). It illustrates the inheritance pattern that occurs in autosomal recessive conditions.

Risk to Family Members

Unaffected parents of an individual with Usher syndrome

Unaffected parents are classed as carriers- carrying a single copy of the same Usher syndrome-causing gene. Carriers are not affected and do not exhibit any symptoms associated with Usher syndrome.

Siblings of an individual with Usher syndrome

As described previously, each child of carrier-parents has a 25% chance of inheriting Usher syndrome, 50% chance of becoming an unaffected carrier and a 25% chance of being unaffected and not being a carrier.  

Children of an individual with Usher syndrome

If an individual with Usher syndrome has a child with another individual who has Usher syndrome with a genuine (or bona fide) mutation in the same Usher gene, then all children will develop the same form of Usher syndrome. 

If an individual with Usher syndrome has a child with an unaffected carrier of the same Usher gene, then the child has a 50% chance of developing Usher syndrome. It is worth noting that carrier testing for Usher syndrome is not widely available, except if the prospective parents are second cousins or more closely related to each other.

 


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Created: February 2016

Review due: February 2018

First published: Wednesday 2 December 2015
Updated: Wednesday 30 November 2016