Hereditary Amyloidosis; The Autosomal Dominant Inheritance Pattern

Image courtesy of https://healthjade.net/transthyretin/

The pattern of how the gene is passed on in hereditary amyloidosis is not gender specific and both male or female are likely to carry the mutated gene if they are predisposed to do so from their parents.

Our human body cell holds 2 copies of each gene, one from each of our parents. Within each cell, the genes are arranged into forty six long strings called chromosomes, and half of it comes from the father and the other half from the mother.  The interaction between both of the halves are the building blocks to how we look externally whereas internally it decides on, for example, what blood group we fall under.  Then there are the sex chromosomes comprising of 2X chromosomes for the women and the XY chromosome for the men.  Diseases that result from a mutation (abnormality) in a gene within a sex chromosome may be passed from parent to child by “sex-linked” inheritance.

All the other 44 chromosomes apart from the X and Y chromosomes are referred to as “autosomes.” Diseases that result from mutations in genes within the autosomes may be passed on from parent to child by “autosomal dominant ” inheritance  or by “autosomal recessive” inheritance.

Most forms of hereditary amyloidosis are inherited by autosomal dominant inheritance.

When there is simple autosomal dominant inheritance of a condition:

  • Each child has a 50% (1 in 2) chance of receiving a mutated copy of the gene from the father.
  • Each child has a 50% (1 in 2) chance of receiving a normal copy of the gene from the father.
  • Half of the children have a mutated gene and develop the disease. They can then pass the mutated gene and the disease on to half of their children.
  • Half of the children have two copies of normal gene. They are healthy and they cannot pass the disease on to their children.
  • Brothers and sisters of people with the disease have a 50% (1 in 2) chance of having the mutated gene and developing disease.
  • Men and women have equal chances of receiving the mutated gene and of developing disease.

Incomplete penetrance

For many of the diseases that are passed on by autosomal dominant inheritance, all people with a mutation in the gene develop disease. However, in the case of the hereditary systemic amyloidosis, this is not the case. An additional genetic principle called incomplete penetrance operates, making the situation more complicated. Incomplete penetrance means that:

  • Some people who inherit a mutated copy of the gene do not develop any amyloid at all.
  • Some people who inherit a mutated copy of the gene develop only a small amount of amyloid and do not suffer from any clinical problems.
  • Some patients diagnosed with hereditary systemic amyloidosis have no family history of the disease.
  • Information about a particular family is important for evaluation of the likelihood that a young healthy person with a mutation will develop disease.

* Some details of information derived from UK Amyloidosis Information Site 

Print Friendly, PDF & Email
Advertisements

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.

 

Eidos AG10 ATTR-CM drug trial recruitment are underway in NZ

Please contact Dr Tim Sutton (timothy.sutton@middlemore.co.nz) or Dr Hugh Goodman (hugh.goodman@waikatodhb.health.nz)

%d bloggers like this: