HHT Genetic Testing

Testing for an unknown mutation

HHT Solutions uses these molecular methods to search for the unique mutation in the ENG gene or ALK1 gene that causes the disease in a family with confirmed clinical diagnosis of HHT:

• Quantitative multiplex PCR identifies deletions, insertions and duplications of genetic material, particularly deletions too large to be detected by sequencing.
• Sequence analysis(sequencing) detects variations in the sequence of nucleotides in the coding regions of the DNA. Deviations from the consensus sequence found in the healthy population are potentially mutations.
• Reverse-transcriptase PCR amplifies the sequence of mRNA instead of DNA. By studying mRNA sequence, we can detect splicing errors that will not be detected by sequencing only the exons of the DNA.

These three different tests are applied to sections of the ENG gene and ALK1 gene in a sequential order determined to minimize the average time to discovery of the mutation and to minimize average cost.

Test Sensitivity

HHT molecular testing is still too new to cite sensitivity figures over a large number of families tested. Data from research studies of a relatively small number of samples suggests that QMPCR and sequencing together detect the mutation in around 75% of families studied. It is not yet known how much sensitivity will be gained from RTPCR, the latest method added to the battery of tests.

Testing for a known mutation

Once the mutation in a family is identified, a single relatively simple test indicates unambiguously whether a blood relative carries the family's mutation or not. Barring human error, the test for a known mutation in a particular kindred is 100% specific.

What is the average turnaround time?

The search for an unknown mutation takes 8-10 weeks for 75% of families. If our methods do not detect the mutation in a family, HHT Solutions stores the samples so that the search may continue as new methods are developed. To test an individual for a mutation already diagnosed in his or her family takes 2-3 weeks.

Who should be tested for mutations that cause HHT?

On the recommendation of a HHT specialist or genetic counselor, HHT Solutions first tests the blood of an individual with a confirmed clinical diagnosis of HHT.

Where are the Referring Specialists?

• More about clinical diagnosis
• HHT treatment Centers in North America
• National Society of Genetic Counselors, searchable directory of genetic counselors in the USA.
• Canadian Association of Genetic Counselors list of counseling centers.

What do the test cost?

Test fees depend on the nature of the clinical diagnosis in each family and vary with exchange rates. Please contact us for current test fees.