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Inheritance

CGD is an inherited disorder, which means that it is passed from parents to their children.

One type of CGD is 'X-linked' (sex-linked) and the other three are 'autosomal recessive'.

But how does this genetic inheritance work exactly?

 

X-linked CGD

Around 60 per cent of people with CGD have X-linked CGD. Everyone with this type is male.

X-linked CGD is caused by an abnormality in the ‘X’ chromosome, part of the set of genes which determine a person’s sex.

This type of the disorder is also called ‘sex-linked CGD’ and it’s why there are more men with CGD than women.

 

How do males get the abnormality?

Every person has two chromosomes that determine their sex. Women have XX chromosomes and men have XY chromosomes.

When a baby is conceived, it gets one of its mother’s X chromosomes. The father can either pass on his X chromosome (making a girl) or his Y chromosome (making a boy).

The CGD gene is ‘recessive’. That means it is only present on one of a woman’s X chromosomes. The other X chromosome contains the healthy gene which allows her to produce white cells that make bleach-like chemicals to fight infection.

So women, with two XX chromosomes, can’t get X-linked CGD.

However, if a woman passes on her faulty X chromosome to her son, who will only have one X chromosome, he will get CGD. There is a 50 per cent chance of him getting the unhealthy X chromosome instead of the healthy one.

 

X-linked CGD carriers

Although girls don’t develop X-linked CGD, they can still be carriers. As mentioned above, if a woman passes her faulty gene to her son, he will develop CGD. If she passes it to her daughter, the daughter will become a carrier too.

A man can also pass his faulty CGD gene on to his daughter, making her a carrier. He won’t pass CGD on to a boy, as he’ll be passing on his Y chromosome.

Carriers seem to be prone to mouth ulcers and certain types of skin rashes.

This diagram below shows how a father with CGD passes on his defective X chromosome (*) to his daughters. But they don’t develop CGD as they have inherited a healthy chromosome from their unaffected mother. They do, however, become carriers:

Father passing X chromosome to daughter

Carrier Daughter Inheritance from Father

This image shows how a carrier mother passes on X-linked CGD to her baby:

How X-linked CGD is inherited

X-linked CGD Inheritance from Mother

 

Autosomal recessive CGD

Defective genes on autosomes (other types of chromosomes aside from chromosomes which determine sex) also cause CGD.

People have two of each autosome in their body, including those with the CGD gene. One comes from their mother and one from their father. As long as one works normally, the person won’t develop CGD.

However, they will be a carrier. That means the CGD gene is ‘recessive’. This is because neutrophils (types of white blood cells that kill bacteria and fungi) need only one good copy of the gene to work well.

For a child to have autosomal recessive CGD, they must have two defective genes – one from each parent.

This image shows autosomal recessive inheritance:

Autosomal Recessive CGD Inheritance

Autosomal Recessive CGD Inheritance

 

Distribution of the different types of CGD

X-linked CGD is the most common type of CGD:

Table of the distribution of different protein types

Distribution of the different CGD proteins

 

Lucinda Brown at our 2012 Family Weekend Conference

Lucinda Brown talks about how CGD is passed between generations and the options available to future parents. Listen here

 

More information

Read more about having children.

Read more about the different types of CGD.

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