What are "Gene Mutations"?

A "mutation" is a change in a gene that prevents it from working properly. A "germline" mutation is a change that occurs in the egg or the sperm, or both, and is passed from one parent or both parents to the child.

Inherited bone marrow failure syndromes (IBMFS) result from mutations, or genetic changes, in one of the many genes which have been found to cause these diseases (see individual syndrome descriptions). These mutations occur in several different patterns within families. These patterns define the specific kind of genetic inheritance by which each disease is transmitted. Examples include:

X-linked recessive inheritance: Females have two X chromosomes (XX), and males have an X and a Y chromosome (XY). Combinations of these two chromosomes determine if a person is to be either male or female. These two chromosomes (the X and the Y chromosomes) are therefore called the "sex chromosomes." If a mutation occurs on one of the mother’s X chromosomes, and if she passes that abnormal X chromosome to her son, who has only one X chromosome, he will have the disease. If he receives the other, unaffected, normal X chromosome from his mother instead, he will not have the disease. Since daughters have two X chromosomes, the normal X chromosome can compensate for the abnormal X chromosome should she inherit it, and so daughters do not have the disease; they are "carriers" of the abnormal gene.

Autosomal recessive inheritance: Each person has a total of 23 pairs of chromosomes. One chromosome from each pair is inherited from a person’s mother, and the other chromosome in the pair is inherited from the person’s father. 22 pairs are called "autosomes", and the other pair is called the sex chromosomes (XX or XY). In order for a person to develop an autosomal recessive disease, they must inherit two abnormal copies of the disease-related gene, one from each parent. Each parent of a patient with an autosomal recessive disease has one copy of the abnormal gene and one copy of the normal gene. As a result, the parents typically have no disease, because the one normal gene is sufficient to prevent disease from developing.

Autosomal dominant inheritance: Disease occurs in the presence of only one mutant chromosome, whose effect is stronger than the effect of the paired normal chromosome. Thus, anyone with one mutant gene is affected. Children of a person with one mutant and one normal gene have a 1 in 2 chance of receiving the mutant gene, and thus having the disease. However, the strength of the effect of the mutant gene is not the same in every person, and thus the appearance of the disease may be of variable severity or even inapparent in someone who carries the mutant gene.

Mitochondrial inheritance: Mitochondria are small structures inside each cell which contain DNA (molecular material). This DNA is separate from the usual DNA found in the nucleus of each cell. Mitochondria produce much of the energy that cells need to function in a normal manner. Mitochondria are passed from mother to child in the mother’s egg. Sperm do not contain mitochondria. Thus, only mothers can pass diseases caused by mutations in mitochondrial DNA to their offspring.