We have two copies of every gene in our bodies, inheriting one from our mother and one from our father. Our genes are located on chromosomes inside the nucleus of each cell. There are 23 pairs of chromosomes. The first 22 pairs are numbered and are the same in males and females. The 23rd pair are the sex chromosomes, with females having two X chromosomes and males having an X and a Y chromosome. Males pass on their X chromosome to all of their daughters and their Y chromosome to all of their sons.
Many genetic diseases are caused by changes or “variants” in a single gene. A variant can cause the gene to not work properly. Whether or not people show signs of a genetic disease depends on how the disease is inherited. X-linked recessive inheritance means the disease happens when a variant occurs in a gene located on the X chromosome. Because men only have one X chromosome, they will likely show symptoms of the disease if they have an X-linked gene variant. They will pass this X chromosome on to all of their daughters, who will be “carriers” of the X-linked gene variant. However, since they only pass on their Y chromosome to their sons, none of their sons would inherit the X-linked gene variant.
Carrier females of X-linked variants are usually healthy with no related symptoms. However, some may show mild symptoms, depending on the specific disease. Each of the sons of a carrier female has a 50% chance of being affected with the disease and each of her daughters has a 50% chance of being a carrier. A female can show full symptoms of an X-linked disease if she has variants in BOTH copies of an X-linked gene.
Knowing about carrier status of an X-linked recessive variant and potential risks of disease can be helpful in discussing family planning and reproductive testing options. Since relatives also have an increased risk of being carriers of a gene variant, this can be important information to share with your family. Many severe X-linked recessive gene variants occur for the first time in one person as a “new mutation”. In this case, there may not be a family history of a disease and screening for these gene variants can be helpful in providing more information about possible risk of a disease in a family.
Through our whole genome sequence (WGS) analysis, we screen for medically significant variants in hundreds of genes, some of which follow X-linked recessive inheritance. Examples of some X-linked recessive diseases that will be screened for through your WGS, include Hemophilia A and B, along with many others. Your genomics reports will specify if you have one or two variants in an X-linked gene, depending on if you are male or female. This report will be reviewed in detail with you by one of our clinicians.
Where can I learn more?
National Society of Genetic Counselors: https://www.nsgc.org/findageneticcounselor
Genetics Home Reference: https://ghr.nlm.nih.gov/
Help Me Understand Genetics: National Library of Medicine (US). Genetics Home Reference [Internet]. Bethesda (MD): The Library; 2018 Apr 3. Inheriting Genetic Conditions; [cited 2018 Apr 3]; Available from: https://ghr.nlm.nih.gov/primer#inheritance. Accessed April, 2018.
Illustration: National Library of Medicine (US). Genetics Home Reference [Internet]. Bethesda (MD): The Library; 2018 May 22. [Illustration] X-linked recessive; [cited 2018 May 22]; Available from: https://ghr.nlm.nih.gov/primer/inheritance/inheritancepatterns.