Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens

Eur J Hum Genet. 2012 Jan;20(1):27-32. doi: 10.1038/ejhg.2011.134. Epub 2011 Aug 3.


Spinal muscular atrophy (SMA) is a leading inherited cause of infant death with a reported incidence of ~1 in 10,000 live births and is second to cystic fibrosis as a common, life-shortening autosomal recessive disorder. The American College of Medical Genetics has recommended population carrier screening for SMA, regardless of race or ethnicity, to facilitate informed reproductive options, although other organizations have cited the need for additional large-scale studies before widespread implementation. We report our data from carrier testing (n = 72,453) and prenatal diagnosis (n = 121) for this condition. Our analysis of large-scale population carrier screening data (n = 68,471) demonstrates the technical feasibility of high throughput testing and provides mutation carrier and allele frequencies at a level of accuracy afforded by large data sets. In our United States pan-ethnic population, the calculated a priori carrier frequency of SMA is 1/54 with a detection rate of 91.2%, and the pan-ethnic disease incidence is calculated to be 1/11,000. Carrier frequency and detection rates provided for six major ethnic groups in the United States range from 1/47 and 94.8% in the Caucasian population to 1/72 and 70.5% in the African American population, respectively. This collective experience can be utilized to facilitate accurate pre- and post-test counseling in the settings of carrier screening and prenatal diagnosis for SMA.

MeSH terms

  • Adult
  • DNA Copy Number Variations
  • Ethnicity / genetics
  • Female
  • Fetus / cytology
  • Gene Frequency
  • Genetic Carrier Screening / methods*
  • Genetic Counseling
  • Genetic Testing / methods
  • Genetic Testing / standards*
  • Genotype
  • Humans
  • Male
  • Muscular Atrophy, Spinal / diagnosis*
  • Muscular Atrophy, Spinal / epidemiology
  • Muscular Atrophy, Spinal / ethnology
  • Muscular Atrophy, Spinal / genetics*
  • Mutation
  • Prenatal Diagnosis / methods
  • Prenatal Diagnosis / standards*
  • Prenatal Diagnosis / statistics & numerical data
  • Reproducibility of Results
  • Sequence Analysis, DNA
  • Survival of Motor Neuron 1 Protein / genetics
  • United States / epidemiology
  • United States / ethnology


  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein