Inherited Genetic Disorders

Single gene defects are caused by single gene abnormalities. This is called a mutation. The mutation may be present on a single chromosome of a pair or on both chromosomes of the pair. Mutations cause an error in the genetic information of the gene that alters the normal function of a cell. Gene mutations can alter the cells function due to a lack of a required protein. Single gene disorders usually show a characteristic family history of a specific genetic disease. Examples include Cystic fibrosis, Sickle cell disease, Fragile X, Thalassemia, and Duchenne muscular dystrophy.

Family History

PGT is recommended for families with a history of a specific genetic disease. Using various techniques, PGT laboratories can examine each developing embryo to identify the absence or presence of these specific genetic disorders. As a result, only those embryos free of genetic disease will be transferred to the patient’s uterus, increasing the chance of a healthy pregnancy.

Single gene disorders are categorized depending upon whether the gene is located on the X chromosome, an autosome or whether the gene is dominant or recessive. These classifications include autosomal recessive, autosomal dominant and X-linked.

Dominant Disorders

For a dominant disorder, one only needs to have the abnormal DNA sequence on one chromosome. If that mutation is passed on to the embryo, the embryo will be affected with that genetic disease. One example of an autosomal dominant disorder is Myotonicdystrophy.

Recessive Disorders

Recessive disorders require that the mutation be present on both chromosomes of the chromosome pair. If one only has the mutation on one chromosome, the individual is normal but carries the mutation in his cells and is called a carrier. The fertilization of an egg from two carrier parents may result in an embryo having the mutation on both chromosomes of the chromosome pair and therefore being affected with that genetic disease. For example, Cystic fibrosis (CF) is a common autosomal recessive genetic disorder that primarily affects the lungs of CF patients. The CF mutation affects a protein within the cell that reduces the cell's ability to function properly. This results in a build up of mucous within the lungs, lung dysfunction and possible death.

X-linked Disorders

X-linked disorders are due to mutations of genes on the X chromosome and have different patterns of inheritance due to their transmission on a sex chromosome and whether the embryo is male or female. Examples of X-linked diseases are the Fragile X syndrome and Duchenne muscular dystrophy.

Genetics 101

What Causes Genetic Defects?

Genes are composed of DNA and provide instructions for the building of proteins that direct the functions of all of our cells. There is controversy over exactly how many genes human have, but 30,000 is a reasonable estimate. These genes are organized on string-like structures called chromosomes.Humans have 23 pairs of chromosomes in each cell – one derived from our father and one from our mother. Genetic disease is caused by abnormalities of gene function. This can occur by having too many or too few chromosomes (aneuploidy), when chromosome pieces are attached to the wrong chromosome (translocation), when one is missing a piece of a chromosome (deletion), when part of a chromosome is upside down (inversion), or when the gene's DNA sequence is changed.

Chromosome Abnormalities

Chromosome abnormalities, such as aneuploidy or structural chromosome rearrangements, are responsible for most genetic diseases. Most cells contain 23 pairs or 46 chromosomes. These include chromosomes 1 to 22 (the autosomes) and chromosomes X and Y (the sex chromosomes). Sperm and eggs only contain 23 single chromosomes (one from each chromosome pair). During fertilization, the embryo receives one chromosome of each pair from each parent resulting in a normal male (46,XY) or a normal female (46,XX). If the sperm or egg harbors a chromosome abnormality, this can be transmitted to the embryo resulting in a genetic disorder.

In the IVF setting and in natural conception, chromosomally abnormal embryos have a low implantation rate and if they do implant, the pregnancy often results in miscarriage or the birth of a baby with physical problems, developmental delay and/or mental retardation. Chromosome disorders occur in well over half of all first trimester pregnancy losses.

Down Syndrome is usually associated with advanced maternal age and is a common example of aneuploidy. Down Syndrome is caused by having an extra #21 chromosome (3 instead of 2). It is also referred to as trisomy 21.

Single Gene Abnormalities

Single gene abnormalities (mutations) are caused by changes in the DNA sequence of a gene. Genes produce proteins that make our cells work properly. Single gene disorders usually show a characteristic family history of a specific genetic disease. Gene mutations can alter the cells normal function due to a lack of a required protein. For example, Cystic Fibrosis (CF) is a common genetic disorder that primarily affects the lungs of CF patients. The CF mutation affects a protein within the cell that reduces the cells ability to function properly. This results in a build up of mucus within the lungs, lung dysfunction and possible death.