Chromosome 15 Disorders

What does human chromosome 15 do? 

This is a common question with a complicated answer.  Each chromosome has hundreds to thousands of genes, depending upon the size of the chromosome. Chromosomes package our genetic information – how we inherit our genes from our parents and pass the genes on to our children.  

Each gene is an instruction to make a protein, and then the protein performs a job or jobs in the body.  One protein may be responsible for a really specific job such as providing structure in the bone or breaking down a certain kind of sugar in food, but many proteins have jobs that affect many body parts, like turning on other genes or communicating with other proteins.   

Chromosome 15 contains more than 600 genes, including genes important to brain function, heart development, hormone control, and essentially every part of our body.  This is typical – every chromosome contains genes that affect every body organ.   

When people have differences in their chromosomes, missing pieces or extra pieces of their chromosomes, then this means that they have missing or extra genes.  The entire set of chromosomes is like a recipe to make an individual.  Some ingredients in a recipe need to be very exact, while other ingredients can have some variability without causing any issues.  Genes and the proteins made from them can be similar – some proteins are needed in very exact amounts while others can vary without causing any issues.  Some missing or extra genes can affect the development of a person, similar to how having missing or extra ingredients can affect the final product of a recipe. 

Who carries chromosome 15? 

People generally have two chromosome 15s, a maternal chromosome 15 from the egg and a paternal chromosome 15 from the sperm.  In most individuals, their chromosome 15s look exactly the same, with the striping pattern shown above in the photo as seen under the microscope.   

What is special about chromosome 15? 

Chromosome 15 is unusual because a section of this chromosome is imprinted.  This means that which genes are turned on depends on whether the chromosome 15 comes from the mother or from the father.  For example, in brain cells, UBE3A is turned on from the maternal chromosome 15 and turned off on the paternal chromosome 15.  On the other hand, the MAGEL2 gene from the father’s chromosome 15 is turned on, while the MAGEL2 gene from the mother’s chromosome 15 is turned off.   

How do you diagnose genetic conditions caused by chromosome 15?

Again, this is a tricky question to answer since it really depends upon the specific condition, and whether that condition is caused by a difference in just one gene or by a difference that affects a group of genes and a section of the chromosome.  Some conditions, like Angelman syndrome, can be especially difficult to diagnose because there are multiple mechanisms (called genotypes) that can cause Angelman syndrome.    

Some tests that may be performed when a chromosome 15 condition is suspected:

What are symptoms of chromosome 15 disorders?   

There are many genetic conditions caused by differences in chromosome 15.  Many genetic conditions cause developmental delays, differences in learning, and risks for certain health issues, but characteristics may vary greatly depending on the specific condition. Some genetic conditions that are caused by differences in the region of chromosome 15q11.2-q13 are:

• Angelman syndrome (AS): Individuals living with Angelman syndrome typically experience developmental disabilities, an increased risk of seizures, and difficulties with verbal speech and balance.  Angelman syndrome has several possible causes but is most often caused by a deletion of the maternal chromosome 15q11.2-q13.1.  For more information, click here: https://cureangelman.org/about-angelman-syndrome.     

• Prader-Willi syndrome (PWS): Individuals living with Prader-Willi syndrome typically experience weak muscles (hypotonia) in infancy, followed by excessive hunger and obesity in childhood, with an increased chance of developmental delays and behavioral issues. PWS has several possible causes but is most commonly caused by a deletion of the paternal chromosome 15q11.2-q13.1.  For more information, click here https://www.pwsausa.org/. 

• 15q11.2-q13.1 duplication (also called Dup15q syndrome): Individuals living with Dup15q syndrome typically have intellectual disabilities, low muscle tone (hypotonia), and an increased risk for seizures, and autism spectrum disorder. Dup15q syndrome is caused by having one or more extra copies of genes from the maternal 15q11.2-q13 region. For more information, click here: https://dup15q.org/ 

• Schaaf-Yang syndrome (SYS): Schaaf-Yang syndrome is a rare genetic disorder that affects learning, physical growth, and behavior.  It is caused by mutations in the MAGEL2 gene and shares some similarities with Prader-Willi syndrome, but it often involves more severe intellectual disability, joint contractures, and a higher likelihood of autism spectrum disorder.  For more information, click here: https://www.fpwr.org/sys-home 

Which conditions are caused by a deletion on chromosome 15? 

Which condition is caused by a deletion depends upon the location of the deletion on the chromosome. A deletion can mean that genes are missing.  It’s the missing gene (or genes) that then cause the characteristics of that condition. 

The most common deletion of chromosome 15 that causes a condition is a deletion of chromosome 15q11.2-q13. This deletion is small and typically cannot be seen under the microscope.  Consequently, it is often called a microdeletion.   

• This deletion causes Angelman syndrome when it occurs on the chromosome 15 from the egg (maternal)  

• This deletion causes Prader-Will syndrome when the deletion occurs on the chromosome 15 from the sperm (paternal).   

Combined, Angelman syndrome and Prader-Willi syndrome probably affect about 1 in 8,000 individuals.  There can be other deletions at different locations on chromosome 15, but these are more rare.  For example, a deletion of chromosome 15q26 has been reported in around 30 individuals worldwide. For more information about other deletions and the characteristics of those deletions, click here: https://rarechromo.org/disorder-guides/. 

Wondering about a possible chromosome 15 condition in yourself or someone you love? 

If you are wondering about a condition caused by chromosome 15, the first step is raising your concern with your or your loved one’s health care team.  The primary care provider will often recommend consulting with a genetics specialist, like a geneticist, to make sure that the appropriate testing is ordered.  In the USA, click here to see Genetics Clinics: https://clinics.acmg.net/.