Genetics

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(Page 5)

Genetics

X-linked recessive:

• Duchenne muscular dystrophy is a very common (1 out of 3,500 male births) disorder that results from the presence of an abnormal muscle protein. Muscles of young boys gradually deteriorate until even the muscles required for normal respiration become ineffective. These boys usually die of pulmonary infections before the age of 20.
• Hemophilia A is seen in 1 out of 10,000 male births. The defective protein (coagulation factor VIII) is required for normal blood clotting. Affected individuals require injections of the protein or transfusion of blood products to prevent internal bleeding. Until recently, when the genetically engineered protein became available, many of these individuals contracted viral hepatitis or AIDS as a result of their many transfusions.

Autosomal dominant:

• Familial hypercholesterolemia (FHC) is a fairly common disorder (1 out of 500 individuals are heterozygous). The affected gene codes for a protein which is found on the external surface of most of the body's cells. This so-called receptor protein mediates the uptake of cholesterol into the cells. This cholesterol is transported in the blood by a lipoprotein called LDL . When LDL can't get into cells, it increases to high levels in the blood. High levels of LDL (with its associated cholesterol) increases the risk of developing arteriosclerosis and coronary artery disease. Homozygous individuals (about 1 out of 1,000,000 births) have extremely high levels of LDL and develop coronary heart disease in childhood.
• Huntington's disease is a neurodegenerative disease which doesn't appear until approximately age 30. It has recently become possible to test for the presence of the abnormal gene at any age. This information may be of great interest to individuals who know they will develop the disease later in life since they may wish to modify their plans in regards to marriage and childbearing. Other individuals prefer not to know as the prognosis is grim and there is no effective treatment.

X-linked dominant:

Only a few, very rare, disorders are classified as X-linked dominant. One of these is hypophosphatemic rickets (also called vitamin D -resistant rickets). In this case a protein in the kidneys is defective. This protein normally transports phosphate from the urinary filtrate back into the blood. Since the amount of phosphate in the blood is much lower than normal, the bones are chronically stimulated to release calcium and phosphate by hormones such as parathormone. This results in fragile and abnormally structured bones.

CHROMOSOMAL DISORDERS

In chromosomal disorders, the defect is due not to a single gene, but to an excess or deficiency of the genes contained in a whole chromosome or chromosome segment.

Down syndrome is the most common chromosomal disorder (1 out of 800). Affected individuals have an extra copy of chromosome 21. This unbalanced set of genes results in mild to moderate mental retardation and numerous physical changes. Other common examples are Klinefelter syndrome (1 out of 1,000 males) and Turner syndrome (1 out of 5,000 females).

MULTIFACTORIAL DISORDERS

Many of the most common diseases which affect humans undoubtedly involve interactions of numerous genes, including coronary heart disease, hypertension, stroke, and various kinds of cancer. These are currently active areas of research.

MITOCHONDRIAL DNA-LINKED DISORDERS

Mitochondria are small organelles present in most of the body's cells which function in the conversion of certain chemicals in our food, in the presence of oxygen, to the common currency of energy inside cells (ATP).

Mitochondria contain their own private DNA. In recent years, more than 20 hereditary disorders have been shown to result from mutations in mitochondrial DNA. Because mitochondria come only from the egg, they are inherited exclusively from the mother.

A person with a mitochondrial disorder may exhibit maternal inheritance (only individuals related by a maternal relative are at risk). Fathers do not pass on the disease.

Mitochondrial disorders can appear at any age with a wide variety of non-specific symptoms and signs. These disorders may cause metabolic disturbances, developmental delay, blindness, hearing loss, heart rhythm problems, short stature, and gastrointestinal problems.

Review Date: 04/20/2005
Reviewed By: Neal Sondheimer, M.D., PhD., Division of Genetics and Metabolism, Children's Hospital of Philadelphia, Philadelphia, PA. Review provided by VeriMed Healthcare Network.