A recently published paper on universal preconception screening should be on internists’ radar as it heralds a potential broad new application for genetics in adult care.

The back story behind the publication of "Carrier Testing for Severe Childhood Recessive Diseases by Next-Generation Sequencing," has been told in the lay press and it is both tragic and compelling.

Craig Benson got interested in carrier screening for recessive genetic conditions after he and his wife found out that their young daughter had Batten disease, a rare neurodegenerative disease affecting about 1 in 100,000 people. Like most people, the Benson family had never even heard of this disease and yet, after their daughter’s diagnosis, both father and mother discovered that they were carriers for a mutation in one of the genes that cause the disease.

Two years ago, Mr.Benson and others formed the Beyond Batten Disease Foundation (BBDF) and found themselves confronting the question of how a carrier screening concept, inspired by the example of Tay-Sachs, could be applied broadly to all recessive genetic diseases.

The January publication by Callum J. Bell, Ph.D., and colleagues, is the outcome of a collaboration between BBDF and the National Center for Genome Resources (NCGR) in Santa Fe, N.M. (Sci. Transl. Med. 2011;3:65ra4).

The concept appears relatively straightforward. With the cost of DNA sequencing now inexpensive enough to consider offering trait carrier screening to prospective parents for the many rare conditions that in aggregate drive significant childhood morbidity and mortality, and since screening could potentially lead to fewer couples having children with devastating autosomal recessive conditions, then perhaps it is time to make this testing widely available to any adult considering future childbearing. The data in Dr. Bell’s paper suggest that DNA-sequence–based testing on approximately 450 genes linked to genetic conditions can be performed accurately and in a cost-effective manner. According to a statement issued by BBDF and NCGR, "The carrier-screening test is expected to become commercially available in the third quarter of 2011."

If this preconceptual screening strategy overcomes hurdles and becomes clinically available this year, this screening will be the first of its kind.

Although the authors cite Tay-Sachs screening and many practitioners are familiar with other preconceptual genetic screening such as for cystic fibrosis, this is different. Two new features of this proposed screening are that its use would not be limited to a defined at-risk group (i.e., an ethnic or racial group with a "high" carrier rate) nor would it use a "common mutation" approach. This approach will seek to find any and all mutations in the genes of interest and will seek to offer it to an unselected population.

The analysis from Dr. Bell and his colleagues suggests that everyone who undergoes the testing will have "positive results" that require review. Such positive results that will require counseling fall into two categories: well-defined "mutations" and variants of unknown significance (VUS). Among the 104 volunteers studied, each individual silently harbored between zero and seven mutations conferring recessive traits (average 2.4) and approximately 11 VUS.

If an individual with a mutation mates with another individual with a mutation conferring one of the same recessive traits, then that couple has a 25% chance with each pregnancy of having a child with the recessive condition in question. Any provider who has ever ordered a single genetic screening test and then dealt with the counseling and other needs of the patient when there is a positive result, can appreciate the mountain of patient care that this kind of testing will generate, with the more than 10 results per patient available to review.

If such testing becomes clinically available later this year, there will still be many unanswered questions related to its use. Among them: What is the rate of false positives and false negatives? Who will provide the counseling for each patient who undergoes the testing? Who will pay for the time spent by the provider discussing the complicated results? What kind of changes in reproductive choices will this testing result in? Will this testing generate significant "downstream" costs related to diagnostic evaluations in healthy adults? Will there be a net cost savings for the health care system when the up-front and downstream costs are balanced against whatever savings are realized with less overall childhood morbidity and mortality?

While the prediction that such tests will be available by the third quarter of 2011 might be overly optimistic, it seems certain that it is coming soon to a medical practice near you, perhaps yours.

This column, "Genetics in Your Practice," regularly appears on the Internal Medicine News Digital Network and in Internal Medicine News, an Elsevier publication. Dr. Murray is the clinical chief of genetics at Brigham and Women’s Hospital and an instructor at Harvard Medical School, Boston. To respond to this column, e-mail him.

Genetic Screening of Prospective Parents