Genetics

Every person starts out life as a single tiny cell. The information that tells the cell how to build a human body is stored in an encyclopedia of information known as the DNA. This encyclopedia is divided into thousands of short chapters, called genes. Each gene contains the information for building one tiny part of the body, like a piece of liver or muscle.

One tiny cell cannot direct the whole operation of building the whole human body. To accomplish this huge task, it copies its entire encyclopedia of DNA for each new cell it produces. Each new cell then focuses on one part of the encyclopedia and uses the information to assist in the building process. Sometimes the machines that copy the genes for new cells make mistakes. Other times, the genes are damaged for unknown reasons. When this happens, the new cells no longer have the right information in the DNA encylopedia to build the body correctly.

Lesch-Nyhan disease is one of many genetic diseases that occur because of an error in a single gene. In the case of Lesch-Nyhan disease, the gene is called hprt. Extensive research efforts have already uncovered many of the genetic errors, known as mutations, responsible for disease. A list of the known mutations can be found in the Research section.

Silent carrier

All males have one X-chromosome, and all females have two X-chromosomes. Males get Lesch-Nyhan disease when there is a mutation of the hprt gene on the X-chromosome. Females do not get the disease because the normal X-chromosome protects them. These females are known as silent carriers, because they carry the disease, but it remains silent.

Females who are carriers can pass the good chromosome or the bad chromosome to their children. If they pass the good one along, their children are healthy. If they pass the bad one along, the result depends on whether they have a boy or a girl. If the bad chromosome is passed along to a daughter, the daughter is normal but becomes a silent carrier like her mother. If the bad chromosome is passed to a son, he gets Lesch-Nyhan disease. Because every boy inherits his X-chromosome from his mother, only mothers can transmit the disease. Fathers cannot pass the disease to their sons.

Lesch-Nyhan boys do not always get their condition from their mothers. In some cases, their mothers do not carry a bad gene, and they are normal. These boys got their disease when a mutation in the hprt gene occurred very early during their development. Genetic testing is required to determine if the mutation came from the mother or not.

HPRT gene

The hprt gene is located on the long arm of the X chromosome, it's exact position is at Xq26.1.

The information in a gene is coded as a chain of four letters (A, G, C, and T), which are abbreviations for four corresponding molecules (adenine, guanine, cytosine and thymine) residues, in a specific order. Body cells use this information to assemble proteins from amino acids. Proteins form the machinery of a cell, and each protein serves a specific function. See here for more information on what the protein HPRT does.

The following table shows the genetic code for the hprt gene and the amino acid sequence for the protein. Using the genetic code, it is possible to predict the amino acid changes for specific mutations. A detailed list of known mutations is available in the Research section.