Expanded Ashkenazi Jewish prenatal testing panel well received


  • Deborah Levenson

But some worry about implications

Anew study of Ashkenazi Jews living in New York City reports that when the study participants were offered an expanded prenatal testing panel that includes 16 genetic diseases, 95% of them accepted it.

Published online July 29 in advance of print in the journal Human Mutation, the study reports carrier frequencies for the disorders, some of which had not been tabulated in large American Jewish study populations.

The research looked at screening among 10,709 American Jewish patients in the metropolitan New York area. They included patients with unknown and mixed ancestry, and non-Jews married to American Jewish spouses. The conditions on the panel are all neurodegenerative or seriously debilitating, most with early demise. They include Canavan disease (CD), cystic fibrosis (CF), familial dysautonomia (FD), Bloom syndrome (BS), Fanconi anemia (FA), Gaucher disease (GD), mucolipidosis type IV (MLIV), Niemann-Pick disease type A (NPD), maple syrup urine disease (MSUD), glucogen storage disease 1a (GSD1a), lipoamide dehydrogenase deficiency (E3), familial hyperinsulinism (HI), nemaline myopathy (NM), and Usher syndrome types I (USH1) and 3 (USH3).

According to lead researcher Ruth Kornreich, PhD, Associate Professor of Genetics and Genomic Sciences at Mount Sinai School of Medicine (MSSM) in New York City, this is the first published study to look at carrier frequencies for mutations that cause HI and to publish large numbers for several other diseases such as USH1 and USH3. She says she hopes her findings can serve as a resource for geneticists and genetic counselors working with the American Jewish population.

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The research looked at screening among 10,709 American Jewish patients in the metropolitan New York area.


According to Dr. Kornreich, study subjects chose the diseases for which they wanted to be screened. After genetic counseling and reading an informative brochure, more than 95% of subjects chose to be screened for all 16 diseases on the panel, including those with lower carrier frequencies and 1 with a lower detection rate. The higher occurring carrier rate conditions included FA, USH1, USH3, E3, and NM, with carrier frequencies ranging from 1 in 100 to 1 in 168. Although the carrier frequency for USH1 was 1 in 147, the MSSM clinic identified a carrier couple, she notes.

The study included more than 100 mutations that cause the 16 disorders. Among the study subjects whose background was 100% American Jewish, 1 in 3.3 was a carrier for one disease and 1 in 24 was a carrier for 2 diseases.Among all subjects, 1 in 3.7 was a carrier for 1 disease.

Carrier frequencies ranged from 1 in 15.2 for Gaucher disease to 1 in 168 for nemaline myopathy. Several of the diseases had similar frequencies to those reported previously, and some differed where the sample sizes were small.

When couples opted for USH1 screening, a disease leading to childhood blindness and deafness, genetic counselors explained that because the detection rate is at least 75% but not greater than 90%, “testing can reduce risk, but not completely.”

Another View of Expanded Testing

Benjamin Wilfond, MD, a bioethicist and Professor of Pediatrics at the University of Washington School of Medicine in Seattle, says that if the goal of expanded screening is to give patients information they find reassuring, then screening for 16 disorders provides a valuable service. But he worries that people who get tested for reassurance “will probably take whatever they are offered” without knowledge about what the tests mean.

Dr. Wilfond notes that his own research has shown that “not 1 single set of criteria” for what diseases are included on Ashkenazi Jewish screening panels. His research has found that the cost of testing for 1 disease typically costs more than a whole panel (Genetics in Medicine 2005;7:185-90). This creates “an incredible financial incentive to do the whole panel that makes it difficult for people to make decisions about screening for individual diseases,” he says in an interview.

But according to Dr. Kornreich, manymajor labs price Jewish panel assays such that tests for single disease tests are less than the panel.

Expanded Ashkenazi Jewish panels are a departure from the early days of prenatal screening among Ashkenazi Jews, Dr. Wilfond points out. Screening began because of concerns about Tay- Sachs disease, which is fatal usually by age 2, with the goal of eradicating the disease. In contrast, screening today often includes conditions that are not nearly as serious.

Genetic Counseling: More Important than Ever

For clinicians and genetic counselors, inclusion of serious and fatal diseases and those withmilder phenotypes in the same panel presents some communication challenges, Dr. Wilfond says. That's because patients tend to believe that all genetic disease is serious, when in reality there's a continuum of morbidity for many of them, he explains.

As the number of diseases on test panels intended for Ashkenazi Jews grows, explaining what risk really means will prove more difficult.

“It's a challenge to explain this variability in Gaucher, which is often mild but can be serious, along with Tay-Sachs disease, which is always fatal and often included on the same panel,” Dr.Wilfond says.

The distinction between a more serious disease like cystic fibrosis, which has a more constrained phenotype, and a more immediately fatal disease like Tay-Sachs, can also be difficult to communicate to patients, he added.

John Mitchell, MD, Director of the Carrier Screening Program at McGill University in Montreal, Canada, questions whether milder mutations of Gaucher disease should even be included on panels, noting that Dr. Kornreich and colleagues report that 93% of couples with pregnancies affected with homozygotes for mild Gaucher mutation N370S chose to continue the pregnancy. While he praises Dr. Kornreich's team for presenting useful data about such screening, he calls for more research on what type of screening for variations causing mild phenotypes is acceptable to American Jews and other populations.

Inclusion of very rare diseases like nemaline myopathy especially increases the need for genetic counseling, Dr. Mitchell says. To give informed consent, patients must understand underlying risks and residual risks of such testing, he adds, noting his worry that couples might suffer anxiety about its results.

Dr. Kornreich, however, says the patients she studied did understand these distinctions. The vast majority of couples ultimately didn't have to face the prospect of a child with a genetic disease, but welcomed the ability to be prepared for potential challenges in case their children did have disorders.