A gene is a segment of DNA that holds the instructions for building the proteins our bodies need to function. A change in these instructions, known as a gene mutation, can be inherited from a parent or acquired during a person’s life. One specific gene where such changes can have health effects is the BCL6 Corepressor, or BCOR gene. A mutation here can disrupt its normal function, leading to a range of health issues that vary in their nature and severity.
The Role of the BCOR Gene
The BCOR gene provides the instructions for producing a protein called the BCL6 corepressor. This protein partners with other proteins to help regulate the activity of other genes. It acts like a dimmer switch for genetic activity, ensuring that certain genes are suppressed or turned off at the appropriate times.
The BCL6 corepressor protein plays a role in embryonic development, guiding the formation of the eyes, heart, skeleton, and teeth. Its regulatory action helps ensure these developmental processes unfold correctly. The protein is also involved in establishing the left-right asymmetry of the body and in managing apoptosis, the process of programmed cell death.
Syndromes Linked to Inherited BCOR Mutations
When a BCOR gene mutation is inherited, it is present in every cell from conception. This type of germline mutation can lead to developmental syndromes. One of the main conditions linked to inherited BCOR mutations is Oculofaciocardiodental (OFCD) syndrome, which occurs almost exclusively in females and affects the eyes, face, heart, and teeth.
Individuals with OFCD syndrome often present with cataracts at birth or in early childhood and may have smaller than average eyes (microphthalmia). Facial features can include a long, narrow face and a broad nasal tip. Heart defects are also common, alongside dental anomalies such as abnormally long roots in the canine teeth, delayed tooth eruption, and missing teeth.
Another condition associated with inherited BCOR mutations is Lenz microphthalmia syndrome (LMS). As its name suggests, a defining feature of LMS is microphthalmia, which can be severe enough to cause blindness. Other characteristics can overlap with OFCD, including skeletal abnormalities and dental issues.
BCOR Mutations and Sarcoma Development
Distinct from inherited syndromes, BCOR mutations can also be acquired later in life. These changes, called somatic mutations, are not inherited and occur in a single cell, which then multiplies. Somatic mutations in the BCOR gene are linked to sarcoma, a type of cancer that affects bone and soft tissues.
A fusion between the BCOR gene and another gene, CCNB3, gives rise to a rare cancer known as BCOR-CCNB3 fusion sarcoma. This cancer primarily affects children and young adults. The fusion creates an abnormal protein that drives uncontrolled cell growth, leading to tumor formation. This process is different from the developmental syndromes caused by an inherited lack of functional BCOR protein.
Genetic Inheritance and Diagnosis
The BCOR gene is located on the X chromosome, which results in an X-linked inheritance pattern. Females have two X chromosomes, while males have one X and one Y. For a condition like OFCD syndrome, a mutation on one X chromosome is enough to cause the disorder in females. The condition is typically lethal in males because they do not have a second, unaltered X chromosome to produce any functional BCOR protein.
Confirming a diagnosis related to a BCOR mutation requires genetic testing. For inherited conditions like OFCD or LMS, this involves DNA sequencing of a blood sample to detect the germline mutation. For suspected BCOR-related sarcomas, the diagnosis is confirmed by analyzing a tissue sample, or biopsy, from the tumor to identify the specific somatic mutation.
Managing Health in BCOR-Related Conditions
There are no cures for conditions caused by BCOR mutations, so management focuses on supportive care and addressing specific symptoms. This requires a coordinated, multidisciplinary team of specialists tailored to the individual’s health issues.
For someone with Oculofaciocardiodental syndrome, regular surveillance allows for proactive treatment like surgically removing cataracts or monitoring heart defects. The care team often includes:
- An ophthalmologist for eye care
- A cardiologist to monitor heart function
- An orthodontist and dental surgeon for complex dental needs
- A geneticist for information and counseling
For a BCOR-CCNB3 sarcoma, an oncologist leads the medical team. Treatment combines chemotherapy, radiation, and surgery to remove the tumor.