USA Surgery Today

In an autosomal (non“sex-linked) dominant (AD) condition, an abnormality in one member of a gene pair is sufficient to cause the condition. Although the strict definition of a dominant condition specifies that the heterozygous individual is indistinguishable from the homozygous-affected individual, this is often not the case. Instead, frequently the homozygote is more severely affected than the heterozygote.

Most dominant conditions involve the formation of structural proteins. Changes in one gene of a pair can result in a phenotype through loss of function, where the abnormal gene produces an absent gene product. Because only one of the pair of genes is working properly, only half of the normal amount of product is formed. Another way that a dominant gene can cause a genetic condition is through a gain of function, where the new protein takes on a deleterious function (9).

Individuals with a dominant condition have a 50% risk of passing the condition on to their offspring, and males and females are affected with equal frequency. Patients with AD conditions often have other affected family members. Families in which an AD condition is segregating often show a vertical pattern of transmission, with multiple generations affected (Fig. 2-1). Because dominant conditions have a wide variability in expression, a parent might not be identified as having the condition unless he or she is carefully examined for minor manifestations. In some cases, neither parent is affected and the child is a new mutation. The frequency of these new mutations increases with increasing paternal age. Rarely, an individual in an autosomal dominant pedigree who must be a carrier of the gene based on the inheritance pattern shows no manifestations. This is termed incomplete penetrance.

An example of a common AD condition is neurofibromatosis 1 (NF1) (MIM 162200), which occurs in 1 in 3,000 births.

The dynamic stage of a cell is the product of continuous changes in the environment, which requires an active mechanism to dispose of molecules that are no longer necessary for the new physiological condition. The process of macromolecule degradation needs to be carefully regulated; otherwise, it results in the collapse of the cell by autodigestion. Two major mechanisms are used by the cell to degrade molecules: lysosomes and proteosomes. Lysosomes are membrane-surrounded organelles containing a large number of lytic enzymes. Proteosomes are exclusively involved in the degradation of cytosolic proteins, in particular those involved in cell signaling. Lysosomes mediate the breakdown of membrane proteins and membranes. Ligands that are bound to surface receptors and internalized by receptor-mediated endocytosis are also degraded in this organelle.