DNA Diagnosis of Porphyria- Important Clarifications
by: Robert Desnick, M.D., PhD.
It has come to our attention that some Porphyria patients have sent their DNA to 23andMe or to other commercial companies, and have gotten results suggesting that they have “DNA confirmed Porphyria”. We are concerned that results from companies other than DNA testing laboratories that have experience in diagnosing porphyrias may provide patients with misleading information.
A major issue with DNA testing is whether a gene alteration (variant or mutation) is pathogenic (disease-causing) or benign (a change in the gene that does not cause or make one at-risk for the disease). For example, 23andMe does NOT do gene sequencing, but does determine if you have various gene alterations in the porphyria genes, all 57 of which are benign, and are not disease-causing but occur in a particular gene in which other lesions are in fact disease-causing. The benign lesions usually are identified by an “#rs” number. These benign changes are quite common but may lead a patient to believe that he/she has one or more porphyrias. They do not affect the heme biosynthetic enzymes, as they are not pathologic lesions. Of the gene lesions that cause disease, over 98% would be identified by gene sequencing as is done for all the Porphyrias at the Mount Sinai Laboratory and four Porphyrias at the Mayo Laboratory.
The Mount Sinai Genetic Testing Laboratory provides Porphyria DNA testing for all eight Porphyrias, and has a full-time Porphyria Genetic Counselor, Dana Doheny, MS, who is available to assist in arranging testing and interpreting the results. Typical time from receipt of sample to result is about two weeks. If the patient has “biochemical-positive” results and a DNA alteration cannot be found, there is a 1-2% chance that the patient has a “cryptic” mutation or a large deletion in the porphyria gene that is difficult to find by sequcning. The Mount Sinai Laboratory will do additional analyses to find the Porphyria gene lesion, if the patient has one.
Mayo Laboratories test for only three of the four Acute Porphyrias and for Erythropoietic Protoporphyria. To our knowledge they provide sequence results, and do not report polymorphisms..
Desiree notes: Dr Desnick is one of the most famous genetisists in the world. In fact, he is one of only three board certified in the US. See what he has to say about 23 and me. etc.