Correct answer = H. The patient has Wilson disease, an autosomal-recessive disorder that decreases copper efflux from the liver because of mutations to the hepatic copper transport protein ATP7B. Some copper leaks into the blood and is deposited in the brain, eyes, kidney, and skin. This results in liver and kidney damage, neurologic effects, and corneal changes caused by the excess copper. Administration of the metal chelator penicillamine is the treatment. [Note: Because zinc is also chelated, supplementation with zinc is common.] Graves disease results in hyperthyroidism. Hereditary hemochromatosis is a disorder of iron overload. Keshan disease is the result of selenium deficiency, whereas selenosis is caused by selenium excess. Menkes syndrome is the result of a systemic deficiency in copper as a result of mutations to ATP7A, an intestinal copper transport protein.
9.10. A 52-year-old female is seen because of unplanned changes in the pigmentation of her skin that give her a tanned appearance. Physical examination shows hyperpigmentation, hepatomegaly, and mild scleral icterus. Laboratory tests are remarkable for elevated serum transaminases (liver function tests) and fasting blood glucose. Results of other tests are pending.
Correct answer = B. The patient has hereditary hemochromatosis, a disease of iron overload that results from inappropriately low levels of hepcidin caused primarily by mutations to the HFE (high iron) gene. Hepcidin regulates ferroportin, the only known iron export protein in humans, by increasing its degradation. The increase in iron with hepcidin deficiency causes hyperpigmentation and hyperglycemia (“bronze diabetes”). Phlebotomy or use of iron chelators is the treatment. [Note: Pending lab tests would show an increase in serum iron and transferrin saturation.]
UNIT VII Storage and Expression of Genetic Information
DNA Structure, Replication, and Repair
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I. OVERVIEW
Nucleic acids are required for the storage and expression of genetic information. There are two chemically distinct types of nucleic acids: deoxyribonucleic acid (DNA) and ribonucleic acid ([RNA] see Chapter 31). DNA, the repository of genetic information (or, genome), is present not only in chromosomes in the nucleus of eukaryotic organisms, but also in mitochondria and the chloroplasts of plants. Prokaryotic cells, which lack nuclei, have a single chromosome but may also contain nonchromosomal DNA in the form of plasmids. The genetic information found in DNA is copied and transmitted to daughter cells through DNA replication. The DNA contained in a fertilized egg encodes the information that directs the development of an organism. This development may involve the production of billions of cells. Each cell is specialized, expressing only those functions that are required for it to perform its role in maintaining the organism. Therefore, DNA must be able not only to replicate precisely each time a cell divides, but also to have the information that it contains be selectively expressed. Transcription (RNA synthesis) is the first stage in the expression of genetic information (see Chapter 31). Next, the code contained in the nucleotide sequence of messenger RNA molecules is translated (protein synthesis; see Chapter 32), thus completing gene expression. The regulation of gene expression is discussed in Chapter 33.
The flow of information from DNA to RNA to protein is termed the “central dogma” of molecular biology (Fig. 30.1) and is descriptive of all organisms, with the exception of some viruses that have RNA as the repository of their genetic information.
II. DNA STRUCTURE