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

By E. Sugarman, N. Nagan, Hui Zhu, V. Akmaev, Zhaoqing Zhou, E. Rohlfs, K. Flynn, B. Hendrickson, T. Scholl, D. Sirko-Osadsa and 1 more. European Journal of Human Genetics, 2011

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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.

Subfields: Genetics, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/a0e209ee0adc61f65c446784bb76a25efdde4bf4

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Citations in the corpus

Prevalence, incidence and carrier frequency of 5q–linked spinal muscular atrophy – a literature review (2017, background): “This was seen in African Americans [46, 62, 77], as well as in Black Africans [66] and would indicate a higher proportion of 2-copy (duplication) alleles, thereby suggesting a higher number of ‘2 + 0’ carriers.”
Current Clinical Applications of In Vivo Gene Therapy with AAVs (2020, background): “This autosomal recessive disorder results from a mutation in the survival motor neuron SMN1 gene with an incidence of approximately 1:10,000 live births, 60% of whom have SMA type 1.(2,3) The human SMN gene is an inverted duplication on chromosome 5q13.”