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What is PCD?

PCD is a disease caused by changes, called mutations, in one of your genes. Genes are subunits of your DNA sequence. You have around 20,000 genes in total across your whole genome (all your DNA sequence), and each of these genes has a different function. Around one thousand genes are required for making the different types of cilia in your body. Mutations in these genes can lead to diseases called ciliopathies. PCD is a type of ciliopathy. Mutations in 1 of 50 known genes can cause PCD. There may be other genes which can cause PCD, we still do not know all of the causes of PCD.

PCD is thought to affect 1 in 15,000 people in the UK and has a higher incidence in certain communities where consanguineous marriage (a union between two individuals who are related as second cousins or closer) are more common.

There are two ways of inheriting PCD

Mostly PCD occurs when both parents of a child are carriers of the condition. In these cases, two copies of the faulty gene are needed to cause the condition. A carrier of a condition has just one copy of a faulty gene. They will usually be unaffected and will therefore not know that they are at risk of having an affected child.

The second way to inherit PCD is when the mutated gene is on the X chromosome so PCD is passed down from the mother. The faulty PCD gene can cause the cilia not to work properly e.g. they may move too fast, too slow, are completely static or are completely missing. Each different gene can cause different type of issues for the PCD patient e.g. some people have really bad sinusitis but good lungs, others have poor lungs and situs inversus. This area of research is still being expanded on all the time to better understand the disease.

Currently in the UK, diagnostic testing can only identify the gene causing a person’s PCD in up to 70% of PCD cases.  To be diagnosed with PCD then you will need to have a combination of tests including nasal biopsy and sometimes genetic tests.  Please see our diagnosis page for more information.

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Understanding Genetics

Humans, like every other organism, are made up of cells. We all start off as just one cell at the time when a sperm, which carries half of our father’s DNA, fertilises an egg, which carries half of our mother’s DNA. We start life as this single cell with one full copy of DNA, half from our mum and half from our dad. As this cell divides, all of the DNA (subunits of which are called genes) is copied so that every new cell possesses a full set of genetic material: the genome. The mechanism of copying the genome is quite remarkable considering that each cell, which is typically less than 1mm in size, contains around two metres of DNA!

What is DNA?

DNA is a type of chemical called a nucleic acid. DNA stands for deoxyribonucleic acid. All of the DNA in your cell, when considered together, is called your genome. Your genome does not consist of one single long DNA molecule, but rather 46 long DNA molecules called chromosomes. You have 23 pairs of chromosomes: one set from your mum and one set from your dad. Along these chromosomes are subunits called genes, which provide a code for making short sections of another type of nucleic acid called RNA. Whereas DNA is a very long-lasting storage molecule which is passed down from generation to generation to generation over millions of years, these RNA molecules are very short-lived templates. RNA is a template for making proteins. Proteins are the building blocks of your cells. For example, one gene will code for an RNA molecule, which will code for a protein such as one of the ‘radial spoke proteins’ which make up part of the cilia in your airways.

Your genome is like a recipe book; with each gene in the genome being like a word in the recipe book. Just as a word in a recipe book tells you which ingredients to mix to make a cake, each gene tells your cells which proteins to make to produce a cilium or other structure in your body.

Just like the words in the recipe book, genes are made up of letters too. Each strand of DNA is formed of four basic building blocks or ‘bases’: adenine (A), cytosine (C), guanine (G) and thymine (T). Sometimes the letters can get swapped, or letters can get added or deleted. This can mean that the code does not make sense anymore, and we make the wrong protein or no protein at all. It is a bit like the letters of your recipe book getting swapped so that you put HAM in the middle of your cake instead of JAM. Just a small 1 letter difference can have a very big effect on how you make your cake. Similarly, just a single letter change in your DNA can have a big impact in how you make a protein, so that your cells and your body work quite differently.

What is a gene?

Genes are sections of DNA that contain the set of instructions to produce one specific molecule in your body; RNA, which usually makes a protein. These proteins control how our body grows and works; they are also responsible for many of our characteristics, such as our eye colour, blood type or height.

The human genome contains around 20,687 protein-coding genes. Different genes or instructions are read at different times in different cells in response to the requirements of our bodies. Each cell contains two sets of genes, one from your mother and one from your father. For ease of storage and access, the genes are packaged up into 46 parcels called chromosomes.

What is a chromosome?

Chromosomes are bundles of tightly coiled DNA located within the nucleus of almost every cell in our body. Humans have 46 chromosomes in their somatic (non-reproductive) cells. We inherit one set of 23 chromosomes from our mother and one set of 23 chromosomes from our father. So we have two sets of 23 chromosomes or 23 pairs.

What is a mutation?

Mutations can occur as a natural consequence of errors in DNA replication or due to exposure to chemicals or radiation (e.g. UV) which cause the DNA to mutate.  They disrupt normal gene activity and cause PCD because the gene is not carrying the correct instructions to the body.

Autosomal recessive inheritance

PCD occurs only when both parents of a child are carriers of the condition. Two copies of the faulty gene are needed to cause the condition. A carrier of a condition has just one copy of a faulty gene. They will usually be unaffected and will therefore not know that they are at risk of having an affected child. A PCD diagnosis normally ‘comes out of the blue’ to families. It is only once a couple have had one affected child that they discover they are at risk of having more affected children. They will have a 25% (one in four) chance of having a child affected by this condition. Additionally, there is a 50% (two in four) chance that their child will be an unaffected carrier.

X-linked recessive inheritance

There are at least 2 ‘X-linked’ forms of PCD (i.e. the mutated gene is on the X chromosome). These are caused by mutations in genes PIH1D3 and RPGR which are on the X chromosome.

These are inherited differently because females have two X chromosomes and males have an X and a Y chromosome.

Because males do not have a second X chromosome, they only need to inherit 1 copy of mutant PIH1D3 or RPGR to develop PCD. They will always inherit this from their mother, because they always get the Y chromosome from their father.

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