Single gene disorders are those that are caused by a genetic mutation(s), or misspelling, of a specific gene, and are passed from parent to child in a particular pattern. The way in which these are passed on is known as an inheritance pattern. The main inheritance patterns are autosomal recessive, X-linked recessive, and autosomal dominant.
An autosomal recessive condition is one that is equally likely to affect both men and women and is caused by having a mutation in both copies of a particular gene. A person with the condition typically inherits a mutation from each of their parents. Having one copy of a gene with a mutation and one normally working copy is known as being a carrier. Carriers usually have no symptoms of the disease. Carrier status is usually detected through a test called carrier screening, or through birth of a child affected with the disorder. If both parents are carriers, they have a 1 in 4, or 25%, chance to both pass the mutation and therefore have a child with the disease. Cystic fibrosis is an example of an autosomal recessive condition. When both members of a couple are carriers for the same autosomal recessive condition, PGT-M may be available.
An X-linked recessive genetic condition is one in which the disease-causing gene is on the X chromosome, one of our sex-related chromosomes. Women have two X chromosomes and men have an X and a Y chromosome. A woman with a mutation in a gene on one X chromosome is known as being a carrier. She typically has no symptoms of the disease, or milder symptoms, as she has a working copy of the gene on her other X chromosome. Men with a mutation in a gene on their X chromosome will have the disease.
Carrier testing for X-linked conditions is therefore typically offered only to women. A woman that is a carrier has a 50% chance to pass the mutation. Sons with the mutation will have the disease, whereas daughters will be carriers like their mother. When a man with an X-linked condition has children and his partner is NOT a carrier for the same, all of his sons are expected to be unaffected while all of his daughters will be carriers. Fragile X syndrome and hemophilia A are examples of X-linked recessive conditions. When a female is a carrier for or a male has certain X-linked recessive conditions, PGT-M may be an option.
An autosomal dominant genetic condition is one that is equally likely to affect both men and women and is caused by having a mutation in only one copy of a particular gene. A person with the condition has a 50% chance to pass the mutation, and therefore the disease, to a child. Huntington disease and neurofibromatosis are examples of autosomal dominant conditions. When an individual has an autosomal dominant condition, PGT-M may be available.
PGT-M (M = monogenic disease) tests for known single gene disorders in the family. Single gene disorders are also known as monogenic (mono=one, genic=gene) diseases. A PGT-M test is created for the specific disease in the individual/couple, and is custom built based on genetic information from that specific family. This test creation process requires DNA samples from the couple, and possibly from some family members.
For convenience, most laboratories request a cheek swab sample, though some may need blood samples. You will likely work with a genetic counselor through this process, whether at your physician’s office, at the testing laboratory, or both. Your genetic counselor will review the test creation process, and assist with collection and shipment of any necessary samples for test preparation.
PGT-M test creation can take a few weeks. The genetic counselor will keep you updated as to the progress of the test creation. In most cases, an IVF cycle is not started until the PGT-M test is complete. Once the PGT-M test is ready, the IVF cycle and embryo testing can begin. Most PGT laboratories in the United States are able to add aneuploidy testing (PGT-A) to the PGT-M test. The embryos will therefore be tested for the genetic disease in the family as well as any sporadic extra or missing chromosomes. Your genetic counselor will be able to discuss how your PGT-M test will be done and if aneuploidy testing can be added.
