Non-Reproductive Symptoms and Health Concerns for Carriers of the c.1624G>T Pathogenic Variant
Carriers of the c.1624G>T (p.G542) CFTR pathogenic variant typically do not experience any non-reproductive symptoms or health concerns, as carriers with only one copy of the pathogenic variant generally do not exhibit clinical manifestations of cystic fibrosis.* 1
Understanding Carrier Status
Cystic fibrosis (CF) is an autosomal recessive disorder, meaning that disease manifestation requires two pathogenic variants (one on each chromosome). The c.1624G>T variant (also known as G542X or p.Gly542Ter) is one of the common pathogenic variants included in the ACMG-recommended minimum panel for CF carrier screening 2.
Key points about carrier status:
- Carriers have only one copy of the pathogenic variant
- A second functional copy of the CFTR gene is sufficient for normal physiological function
- Clinical manifestations of CF require mutations in both copies of the CFTR gene
Health Implications for Carriers
Unlike some other genetic conditions where carrier status may be associated with mild symptoms or increased risks for certain conditions, current evidence does not support any non-reproductive health concerns for CFTR carriers:
- No respiratory symptoms
- No pancreatic insufficiency
- No increased risk for pulmonary infections
- No evidence of sweat gland dysfunction
- No gastrointestinal manifestations
This is consistent with the autosomal recessive inheritance pattern of CF, where carriers maintain sufficient CFTR protein function through their one normal gene copy 1.
Reproductive Considerations
While there are no direct health concerns for carriers themselves, the primary implication of carrier status is reproductive:
- Carriers have approximately a 1 in 4 chance of having a child with cystic fibrosis if their reproductive partner is also a carrier
- Genetic counseling is recommended to understand reproductive risks and options
- Reproductive options may include preimplantation genetic testing, prenatal diagnosis, or use of donor gametes if both partners are carriers 1
Special Considerations
Male Carriers and Fertility
Unlike some other CFTR variants that have been associated with congenital bilateral absence of the vas deferens (CBAVD) in male carriers, there is no specific evidence suggesting that the c.1624G>T variant causes fertility issues in male carriers 2.
Carrier Testing in Family Members
The ACMG recommends genetic counseling for all individuals who have a family history of CF and for all identified CFTR carriers 2. Testing of at-risk family members may be appropriate to determine their carrier status.
Conclusion
Based on current evidence, carriers of the c.1624G>T pathogenic variant in the CFTR gene do not experience non-reproductive symptoms or health concerns. The primary implication of carrier status relates to reproductive risk assessment and family planning.