04/24/2026
As many of you know I had already received genetic testing back in 2014 that confirmed Stickler Syndrome Type 1. However my symptoms have always presented more severe and abnormally compared to more individuals with the same type. Because of this and my children’s new diagnoses (outside of just sticklers), I was offered full genome sequencing through our genetics team. Genetic testing has come a long way since 2014 so we were hopeful we would get answers and on Tuesday we finally discovered why my Sticker Syndrome presents differently compared to most!
When I received my genetic results, they showed a variant in the COL2A1 gene written as c.1414G>T, p.E472*. The COL2A1 gene is responsible for producing type II collagen, a protein that helps form the structure of connective tissues in the body, including the eyes, joints, ears, and parts of the face. Changes in this gene are the most common cause of Stickler syndrome type 1. In my case, the laboratory classified the variant as likely pathogenic. In medical genetics, this classification follows guidelines from the American College of Medical Genetics and Genomics and means there is greater than 90 percent confidence that the variant is disease causing. (based on my symptoms we already know that it is definitely disease causing)
The specific type of change identified in my gene is called a nonsense mutation. This means the mutation introduces what scientists call a premature stop codon. Normally, genes act like instructions for building proteins step by step. My variant causes those instructions to stop early at position 472 of the protein. Instead of finishing the entire collagen protein, the body encounters a stop signal too soon. A helpful way to imagine this is like following a recipe that suddenly says stop halfway through baking a cake. The cake never finishes baking because the instructions ended too early.
When a premature stop signal occurs, cells often activate a protective process called nonsense mediated decay. This is a natural quality control system that detects faulty genetic instructions and destroys them before they can produce a damaged protein. In other words, instead of making a shortened or defective collagen protein, the body often destroys the message entirely. This results in what geneticists call a loss of function variant, meaning one copy of the gene is no longer able to do its job.
Loss of function in the COL2A1 gene is a well established mechanism that causes Stickler syndrome. Humans typically have two copies of most genes, one from each parent. In conditions like Stickler syndrome, having only one working copy of the gene can be enough to produce symptoms. Scientists call this haploinsufficiency, which simply means one copy of the gene does not provide enough protein for normal function. An everyday example would be trying to run a two engine airplane with only one working engine. The plane may still fly, but it may not perform the way it was originally designed.
Another important detail is where the mutation occurs within the gene. The COL2A1 gene contains many sections called exons, and my variant occurs in exon 22 out of 54. Because the stop signal appears relatively early in the gene, the cell recognizes the message as faulty and removes it through the nonsense mediated decay process. This means my body likely does not produce a shortened collagen protein from that copy of the gene at all. Instead, it relies entirely on the remaining working copy of the gene to produce type II collagen.
Another interesting detail in my report is that this specific variant has not previously been reported in major genetic databases such as ClinVar or the Genome Aggregation Database. These databases contain genetic information from large numbers of people and are used by scientists to see how common certain variants are. When a variant is not found in these databases, it usually means it is extremely rare or newly discovered. This does not mean it is harmless. In fact, when a rare variant clearly disrupts an important gene like COL2A1, it often supports the idea that it is disease causing.
Because my mutation appears to be rare and causes the gene to stop working earlier than it should, my presentation of Stickler syndrome may not look exactly the same as someone whose mutation occurs in a different part of the gene. Genetic conditions can vary widely even when they involve the same gene. The location of the mutation, how the body handles the altered genetic message, and other genetic or environmental factors can all influence how symptoms appear in each person. Some mutations in this gene produce abnormal collagen that interferes with normal collagen fibers, while others, like mine, reduce the total amount of collagen available in the body. Both mechanisms can lead to connective tissue differences, but they may affect people in different ways.
Even though my mutation likely prevents the production of a faulty collagen protein, it also means my body is functioning with only about half the normal amount of type II collagen. Type II collagen plays a major structural role in cartilage, the vitreous gel of the eye, parts of the inner ear, and certain skeletal tissues. When there is less of this collagen available, those tissues may have less structural support and resilience over time. A simple way to picture this is to imagine building a suspension bridge with half the usual number of support cables. The bridge may still stand and function, but the structure has less reserve strength when stress is placed on it.
In simple terms, my results show that my body has one copy of the COL2A1 gene that stops working partway through building the collagen protein. The cell’s quality control system likely removes that message before the protein can be made, leaving my body with only one fully working copy of the gene. That reduced collagen production is what leads to the features of Stickler syndrome. Because my specific mutation appears to be rare and previously unreported, and because genetic conditions can vary widely from person to person, it may help explain why some aspects of my experience with Stickler syndrome appear more severe or somewhat different than what many people expect when they read the typical description of the condition.
Genetics is fascinating, and I’m glad to be a part of the research for Stickler Syndrome!
It is important to understand that taking collagen supplements will not correct this type of genetic change. The issue is not that my body lacks access to collagen as a nutrient, but that one copy of the gene responsible for producing type II collagen is not functioning properly. Collagen supplements are broken down into amino acids during digestion, just like any other protein, and they do not travel directly to connective tissues as intact collagen. Because of this, they cannot replace or repair the missing genetic instructions needed to produce type II collagen within the body. While general nutrition is always important for overall health, supplements, creams, etc cannot override or fix a loss of function mutation at the genetic level.
