Huntington’s disease: The Cause

Huntington’s disease is a familial disease, passed from parent to child through a mutation or misspelling in the normal gene, the basic biological unit of heredity. Only an abnormal gene produces HD. Genes are made up of deoxyribonucleic acid (DNA), a molecule shaped like a spiral ladder. Each rung of this ladder is made up of two paired chemicals called bases. Basically, there are four types of bases - adenine, thymine, cytosine, and guanine - each abbreviated by the first letter of its name: A, T, C, and G. Specific bases always "pair" together, and different combinations of base pairs join to form coded messages. A gene is a long string of DNA in various combinations of A, T, C, and G. This unique combination details the gene's function, much like letters join together to form words. Each person has approximately 30,000 genes - a billion base pairs of DNA or bits of information repeated in the nuclei of human cells - which determine individual characteristics or traits.

Genes are grouped in precise locations along 23 rod-like pairs of chromosomes. A chromosome from each pair comes from an individual's mother, the other from the father. Every half of a chromosome pair is similar to the other, except for one pair, which determines the sex of the individual. A gene has two X chromosomes in females and one X and one Y chromosome in males. Specifically, the gene that produces HD lies on chromosome 4, one of the 22 non-sex-linked, or "autosomal," pairs of chromosomes, placing men and women at equal risk of acquiring the disease.

The effect of a gene depends partly on whether it is dominant or recessive. It is only one of the paired chromosomes is required to produce its called-for effect if a gene is dominant. Parents must give chromosomal copies for the trait to be present if the gene is recessive. HD is also called an autosomal dominant disorder because only one copy of the defective gene, inherited from one parent, is necessary to produce the disease.

The genetically transferred defect responsible for HD is a small sequence of DNA on chromosome 4 in which several base pairs are repeated many, many times. Basically, normal gene has three DNA bases, composed of the sequence CAG. The sequence CAG abnormally repeats itself dozens of times in people with HD. This may continue over time, and with each successive generation, the number of CAG repeats may expand further.

Each parent possesses two copies of every chromosome but gives only one copy to each child. Each child who has an HD parent has a 50-50 chance of inheriting the HD gene. If a child has not inherited the HD gene, he or she will not develop the disease and cannot pass it to subsequent generations. An individual who inherits the HD gene, and survives long enough, will sooner or later develop the disease. To some families, all the children may inherit the HD gene; in others, none do. Whether a child inherits the gene has no bearing on whether others will or will not share the same fate.

If one parent of a child has Huntington’s chorea and the other has none, the child has a 50 percent chance of inheriting the disease. Once transmitted, it is certain to develop the first symptoms usually appear between the ages of 35 to 55, but earlier or later occurrences are known. The disease may continue for 10 to 20 years, until the patient dies.