The Science of PKD

General Information About Inheritance

• Human beings have 23 pairs of chromosomes.  One chromosome of the pair comes from the mother and the other chromosome comes from the father.  Figure 1
• Chromosomes are made of gene pairs containing deoxyribonucleic acids (DNA).
• What deoxyribonucleic acids are present and how they are arranged along the gene code for proteins the cells need to grow and function.
• Genes can be dominant, recessive or co-dominant.
• A dominant gene means that disease trait appears when only one gene of the gene pair is mutated.
• A recessive gene means that disease trait appears only when both genes of the pair carry the mutation.
• Co-dominant genes mean that each gene can affect the trait.  Example:  A brown-eyed man and a blue-eyed woman have a child with hazel eyes.

Autosomal dominant polycystic kidney disease – ADPKD

• 85% of mutations in ADPKD occur in chromosome 16 (PKD1 gene).  This gene pair makes a protein called polycystin-1 (PC-1). Figure 2
• 15% of mutations in ADPKD occur in chromosome 4 (PKD2 gene).  This gene pair makes a protein called polycystic-2 (PC-2). Figure 2
• Research has shown that the PC-1 and PC-2 proteins interact in kidney cells and affect cell growth and function.
• There is a family history of the disease.
• Only one mutated gene of the pair is required for the disease to occur.  The mutated gene can come from either parent.
• Every child carrying one mutated gene will have ADPKD.
• Every conception carries a 50% chance of the child inheriting the mutated gene and having ADPKD. Figure 3

Autosomal recessive polycystic kidney disease – ARPKD

• ARPKD results from a mutation in chromosome 6 (PKHD gene).  This gene pair makes a protein called fibrocystin or polyductin. 
• Both genes of the pair must carry the mutation for the disease to occur.
• There is no family history of the disease because each parent carries only one mutated gene.
• Each conception carries a 25% chance of the child inheriting both mutated genes and having ARPKD. Figure 4

What is a cyst and how is it formed?

Two basic processes are involved in the formation of cysts:  Cell proliferation and fluid secretion.

Cell proliferation means that a kidney cell carrying the PKD mutation grows and then divides into two identical daughter cells.  This process continues, one cell into two, two cells into four, and so on, to form the wall of a cyst.  Since the cells being formed are all identical, this is called clonal growth.  Eventually the cyst becomes large enough and pinches off from the kidney tubule. 

Fluid secretion is the process by which the cyst fills with fluid.  Cellular mechanisms move sodium and chloride ions from the cell into the cyst, and water follows, forming the cyst fluid.

Figure 1 - A normal male karyotype. A female would have two X's instead of an X and Y.

Figure 2

Figure 3

Figure 4