SINGLE-GENE
DISORDERS Disorders caused by the mutation of a single gene are often called inborn errors of metabolism
because they reflect alterations of a biochemical pathway. Many inborn errors of metabolism are fatal in early childhood or make maintenance of proper body function difficult if not impossible.
Autosomal Dominant Genes
Autosomal dominant genes, of which more than 4,000 are fully identified, are expressed in both heterozygous and homozygous individuals. Many are lethal when the individual is homozygous. Dominant traits are usually expressed equally in both the male and the female. If one parent is affected, each pregnancy involves a 50% risk of recurrence. The sex of the parent contributing the gene can also play a role in the course of the disease (see genetic imprinting). An example of an autosomal dominant trait is achondroplasia, in which the person's arms and legs are noticeably shortened, but whose trunk and head are of normal size. Fetuses that receive the achondroplasia gene from both parents are severely deformed and die shortly after birth.
Autosomal
Recessive Genes
Autosomal recessive traits, of which 1,700 are fully identified, are expressed phenotypically only in homozygotic individuals. Heterozygotic individuals are known as carriers because they can transmit the gene to their children, who manifest the disease. Usually, affected children will have unaffected carrier parents. Frequently, parents who are closely related transmit autosomal recessive
disorders. The recurrence risk for heterozygous parents is 25% for each pregnancy. Tay-Sachs disease is an example of autosomal recessive disorders. In Tay-Sachs disease the affected gene does not produce an enzyme needed to metabolize lipids. As a result they build up in the brain, causing neurologic deterioration and eventually death. Other such disorders include sickle-cell disease, galactosemia, phenylketonuria, and thalassemia.
Sex-Linked Recessive Genes
In most cases of sex-linked recessive traits, of which 400 are fully identified, the mother is a carrierÑheterozygous but unaffected. She has a 50% chance of producing affected sons through transmission of an X chromosome carrying the gene mutation. Her daughters have a 50% chance of being heterozygous. If an affected male is able to reproduce and marries a homozygous normal female, none of his children will be affected, but all of his daughters will be heterozygous for the sex-linked gene. His sons do not inherit the disease.
Muscular dystrophy and hemophilia are sex-linked recessive disorders. In muscular dystrophy male children have weakness and degeneration of their muscles, progressing from extremities to the entire body. Hemophilia is characterized by severe hemorrhaging and the inability of the blood to clot and heal a wound.
Sex-Linked Dominant Genes
Only a few disorders with sex-linked dominant inheritance are known, such as vitamin D-resistant rickets, which may produce severe bowing of the legs. Mutations occur on the X chromosome, so if the female carries the mutation, recurrence risks are 50% for both female and male progeny; if the male has the disorder, no sons but all of the daughters will be affected.