Understanding Positive Heterozygous Electrophoresis Results
A positive heterozygous electrophoresis result indicates that an individual carries one copy of a genetic mutation and one normal copy of the gene, meaning they have two different alleles (variants) of the same gene. 1
Key Characteristics of Heterozygous Results
- Heterozygous results appear as two peaks or bands on electrophoresis - one representing the normal (wild-type) sequence and one representing the mutant sequence 1
- In dot-blot hybridization techniques, a heterozygous result shows positive signals on both the wild-type and mutant filters 1
- In automated fluorescent detection systems, heterozygous samples show two peaks (normal and mutant) at approximately half the intensity of homozygous peaks 1
Clinical Significance of Heterozygous Results
- A heterozygous result typically indicates carrier status for a recessive condition, meaning the individual carries the mutation but is not affected by the disease 1
- For autosomal recessive conditions like cystic fibrosis, carriers (heterozygotes) generally do not show symptoms but can pass the mutation to offspring 1
- For certain mutations, even heterozygous status may have clinical implications depending on the specific variant detected 1
Example of Interpretation: Cystic Fibrosis Testing
When a heterozygous result is detected in CF testing:
- The laboratory report will specify which mutation was identified (e.g., "DF508 heterozygote") 1
- The interpretation typically states: "One copy of the [specific] mutation was identified, indicating that this individual is a carrier for cystic fibrosis" 1
- Carrier testing is recommended for relatives and reproductive partners of known carriers 1
Special Considerations for Certain Mutations
Some mutations require additional interpretation when found in heterozygous form:
- For R117H mutation in CF testing, the clinical significance depends on whether it's accompanied by other variants like 5T 1
- The position of mutations relative to each other (cis/trans configuration) can significantly affect clinical interpretation 1
- Follow-up testing of parents may be needed to determine the exact configuration of certain mutation combinations 1
Residual Risk Assessment
- A negative test does not completely rule out carrier status, as tests only screen for common mutations 1
- Residual risk calculations after testing depend on ethnicity and family history 1
- For example, after a negative CF carrier test, residual risk ranges from 1 in 140 for European Caucasians to 1 in 930 for Ashkenazi Jewish individuals 1
Potential Sources of Error
- Trace contamination of PCR reactions can lead to false results 1
- Rare genetic variants may interfere with analysis 1
- Failure of one allele to amplify can lead to false homozygous results 1
- Apparent homozygosity should be confirmed by alternative methods, especially for unexpected results 1
Importance of Genetic Counseling
- Genetic counseling is recommended for individuals with heterozygous results to explain implications for family planning 1
- Counseling should address residual risks and the possibility of variants not detected by testing 1
- For certain complex mutations, specialized genetic counseling is particularly important to explain variable phenotypes 1