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

Authors

  • Stuart A. Scott,

    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University, New York, New York
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  • Lisa Edelmann,

    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University, New York, New York
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  • Liu Liu,

    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University, New York, New York
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  • Minjie Luo,

    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University, New York, New York
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  • Robert J. Desnick,

    Corresponding author
    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University, New York, New York
    • Dean for Genetics and Genomics, Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, Fifth Avenue at 100th Street, Box 1498, New York, NY 10029
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  • Ruth Kornreich

    Corresponding author
    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University, New York, New York
    • Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1497, New York, NY 10029
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  • Communicated by David S. Rosenblatt

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. Hum Mutat 31:1–11, 2010. © 2010 Wiley-Liss, Inc.

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