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Differences in SMN1 allele frequencies among ethnic groups within North America
  1. Brant C Hendrickson (brant.hendrickson{at}genzyme.com)
  1. Genzyme Genetics, United States
    1. Colin Donohoe
    1. Genzyme Genetics, United States
      1. Viatcheslav R Akmaev
      1. Genzyme Genetics, United States
        1. Elaine A Sugarman
        1. Genzyme Genetics, United States
          1. Paul Labrousse
          1. Genzyme Genetics, United States
            1. Leonid Boguslavskiy
            1. Genzyme Genetics, United States
              1. Kerry Flynn
              1. Genzyme Genetics, United States
                1. Elizabeth M Rohlfs
                1. Genzyme Genetics, United States
                  1. Andrew Walker
                  1. Genzyme Genetics, United States
                    1. Bernice Allitto
                    1. Genzyme Genetics, United States
                      1. Christopher Sears
                      1. Children's Hospital, Boston, United States
                        1. Thomas Scholl (thomas.scholl{at}genzyme.com)
                        1. Genzyme Genetics, United States

                          Abstract

                          Background: Spinal Muscular Atrophy (SMA) is the most common inherited lethal disease of children. Various genetic deletions involving the bi-allelic loss of SMN1 exon 7 are reported to account for 94% of affected individuals. Published literature places the carrier frequency for SMN1 mutations between 1 in 25 and 1 in 50 in the general population. Although SMA is considered to be a pan-ethnic disease, carrier frequencies for many ethnicities, including most ethnic groups in North America, are unknown.

                          Objectives and methods: To provide an accurate assessment of SMN1 mutation carrier frequencies in African American, Ashkenazi Jewish, Asian, Caucasian, and Hispanic populations, more than 1000 specimens in each ethnic group were tested using a clinically validated, quantitative real-time PCR assay that measures exon 7 copy number.

                          Results: The observed one-copy genotype frequency was 1 in 37 (2.7%) in Caucasian, 1 in 46 (2.2%) in Ashkenazi Jewish, 1 in 56 (1.8%) in Asian, 1 in 91 (1.1%) in African American, and 1 in 125 (0.8%) in Hispanic specimens. Additionally, an unusually high frequency of alleles with multiple copies of SMN1 was identified in the African American group (27% compared to 3.3% – 8.1%). This latter finding has clinical implications for providing accurate adjusted genetic risk assessments to the African American population.

                          Conclusions: Differences in the frequency of SMA carriers were significant among several ethnic groups. This study provides an accurate assessment of allele frequencies and estimates of adjusted genetic risk that were previously unavailable to clinicians and patients considering testing.

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