Carrier screening in Gaucher disease: reproductive decision-making in couples with mixed heritage

Abstract

Mutational analysis provides accurate assessment of Gaucher risk for reproductive decision-making in Eastern European Ashkenazi Jews as a small number of mutations account for most of the mutant alleles. More than 30% of the GD allcles correspond to a variety of rare mutations in other populations.

Carriers of known GD mutations who had a non-Jewish partner were ascertained through a screening program at New York University Medical Center. Each couple was recalled for counseling, results were reviewed and testing offered to the non-Jewish partner. Options included carrier testing by mutation analysis and/or enzymatic analysis and prenatal diagnosis.

We report the choices of the first twelve couples with a mixed heritage after learning that the Jewish partner was a Gaucher carrier. They included 3% of the total couples screened during the last year. Eleven of those couples were in a pregnancy; seven of the non-Jewish partners were male and five were female; five non-Jewish partners had both DNA and enzyme analysis; two chose enzyme analysis alone and another one had DNA screening only; finally, one couple had no additional testing; three couples elected prenatal Gaucher disease determination by amniocentesis with enzyme analysis; none of the non-Jewish partners were determined to be carriers; all of these pregnancies are ongoing but outcomes will be monitored for any affected infant. This study concludes that screening for Gaucher disease in couples with a mixed heritage is feasible. Guidelines for screening couples with mixed heritage need to be established. Both DNA and enzyme analysis should be performed on non-Jewish partners. Prenatal diagnosis should be offered for a definitive diagnosis.