Experience with carrier screening and prenatal diagnosis for 16 Ashkenazi Jewish genetic diseases

Hum Mutat. 2010 Nov;31(11):1240-50. doi: 10.1002/humu.21327.

Abstract

The success of prenatal carrier screening as a disease prevention strategy in the Ashkenazi Jewish (AJ) population has driven the expansion of screening panels as disease-causing founder mutations have been identified. However, the carrier frequencies of many of these mutations have not been reported in large AJ cohorts. We determined the carrier frequencies of over 100 mutations for 16 recessive disorders in the New York metropolitan area AJ population. Among the 100% AJ-descended individuals, screening for 16 disorders resulted in ∼1 in 3.3 being a carrier for one disease and ∼1 in 24 for two diseases. The carrier frequencies ranged from 0.066 (1 in 15.2; Gaucher disease) to 0.006 (1 in 168; nemaline myopathy), which averaged ∼15% higher than those for all screenees. Importantly, over 95% of screenees chose to be screened for all possible AJ diseases, including disorders with lower carrier frequencies and/or detectability. Carrier screening also identified rare individuals homozygous for disease-causing mutations who had previously unrecognized clinical manifestations. Additionally, prenatal testing results and experience for all 16 disorders (n = 574) are reported. Together, these data indicate the general acceptance, carrier frequencies, and prenatal testing results for an expanded panel of 16 diseases in the AJ population.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Female
  • Founder Effect
  • Gene Frequency
  • Genes, Recessive
  • Genetic Carrier Screening / methods*
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / prevention & control*
  • Genetic Testing / methods*
  • Humans
  • Jews / genetics*
  • Male
  • New York City
  • Patient Acceptance of Health Care
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Risk Factors