PAX5 Deficiency – Definition
PAX5 deficiency or a predisposition to ALL 3 (OMIM #615545) is a genetic disease caused by pathogenic variants in the PAX5 gene. Those suffering from it have an increased risk of developing B-ALL. Other hematological diseases or solid tumors have not been described to date.
Synonym:
Predisposition to ALL 3
Gene:
PAX5
Gene product:
PAX5 (paired box protein 5)
Function:
Transcription factor that regulates the differentiation of B cells
Pattern of inheritance:
Autosomal dominant
Prevalence:
Unknown
Genotype-phenotype correlation
The p.G183S missense mutation has so far been found in all known leukemia patients who are carriers of a pathogenic PAX5 variant. However, there is also proof that the missense mutation is present in phenotypically healthy people with a pathogenic PAX5 variant. There is reduced transcriptional activity which points to a partial loss-of-function.
Penetrance:
Incomplete
PAX5 Deficiency – Diagnosis
Clinical Diagnostics
The possibility of a pathogenic PAX5 variant should be considered and tested for genetically in families with multiple cases of acute lymphoblastic B-cell leukemia (B-ALL) and when a somatic 9p deletion has been genetically diagnosed as part of the ALL diagnosis.
Genetic Diagnostics
The diagnosis of “PAX5 deficiency” is confirmed by detection of a pathogenic germline variant PAX5 by single-gene analysis or the use of panel studies consisting of multiple genes.
Differential Diagnoses
- B-ALL with another underlying pathogenic variant
Clinical Presentation
The only clinical manifestation of a pathogenic PAX5 variant described to date is acute lymphoblastic B-cell leukemia or pre-B-ALL. In all of the patients, the leukemia was diagnosed during childhood, which suggests that the risk of developing B-ALL greatly decreases after the first decade of life.
PAX5 deficiency exhibits incomplete penetrance, meaning that carriers of the pathogenic PAX5 variant may be phenotypically healthy – in other words, not suffering from B-ALL.
Other types of hematological neoplasia or solid tumors have not yet been observed in connection with pathogenic PAX5 variants.
Special Features of Treatment
Treatment of B-ALL in patients with a pathogenic PAX5 variant should be discussed thoroughly with the corresponding study center.
When a stem cell transplant is planned with an HLA-compatible sibling as the donor, he or she should first undergo a pathogenic PAX5 variant analysis to rule out the possibility of being an asymptomatic carrier of the same genetic syndrome.
Diagnosis of PAX5 Deficiency- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis of PAX5 Deficiency - What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Recommendations for Early Detection in Your Patients
Since PAX5 deficiency is a rare disease, there is insufficient data to provide standardized surveillance recommendations.
As with other leukemia predisposition syndromes, the following examinations should be conducted regularly:
- Clinical examinations
- Complete blood count once a year
- Bone marrow puncture only with unstable blood values / clinically suspected leukemia
PAX5 Deficiency – Further Information
Support Groups
Unfortunately, we are currently not aware of any support groups for patients with PAX5 Deficiency. New information will be added as soon as it becomes available.
