Carrier screening for spinal muscular atrophy (SMA) in 107,611 pregnant women during the period 2005-2009

A prospective population-based cohort study

Yi Ning Su, Chia Cheng Hung, Shin Yu Lin, Fang Yi Chen, Jimmy P.S. Chern, Chris Tsai, Tai Sheng Chang, Chih Chao Yang, Hung Li, Hong Nerng Ho, Chien Nan Lee

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background: Spinal muscular atrophy (SMA) is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25-50) as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program. Methods and Findings: This is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1) pregnant women were tested for SMA heterozygosity; (2) if the mother was determined to be heterozygous for SMA (carrier status), the paternal partner was then tested; (3) if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10%). The negative predictive value of DHPLC coupled with MLPA was 99.87%. The combined method could detect approximately 94% of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49%) and SMA was diagnosed in 12 (27.91%) fetuses. The prevalence of SMA in our population was 1 in 8,968. Conclusion: The main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling.

Original languageEnglish
Article numbere17067
JournalPLoS ONE
Volume6
Issue number2
DOIs
Publication statusPublished - Mar 7 2011

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Survival of Motor Neuron 1 Protein
Screening
Testing
Genes
Population Genetics
Costs

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Carrier screening for spinal muscular atrophy (SMA) in 107,611 pregnant women during the period 2005-2009 : A prospective population-based cohort study. / Su, Yi Ning; Hung, Chia Cheng; Lin, Shin Yu; Chen, Fang Yi; Chern, Jimmy P.S.; Tsai, Chris; Chang, Tai Sheng; Yang, Chih Chao; Li, Hung; Ho, Hong Nerng; Lee, Chien Nan.

In: PLoS ONE, Vol. 6, No. 2, e17067, 07.03.2011.

Research output: Contribution to journalArticle

Su, Yi Ning ; Hung, Chia Cheng ; Lin, Shin Yu ; Chen, Fang Yi ; Chern, Jimmy P.S. ; Tsai, Chris ; Chang, Tai Sheng ; Yang, Chih Chao ; Li, Hung ; Ho, Hong Nerng ; Lee, Chien Nan. / Carrier screening for spinal muscular atrophy (SMA) in 107,611 pregnant women during the period 2005-2009 : A prospective population-based cohort study. In: PLoS ONE. 2011 ; Vol. 6, No. 2.
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title = "Carrier screening for spinal muscular atrophy (SMA) in 107,611 pregnant women during the period 2005-2009: A prospective population-based cohort study",
abstract = "Background: Spinal muscular atrophy (SMA) is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25-50) as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program. Methods and Findings: This is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1) pregnant women were tested for SMA heterozygosity; (2) if the mother was determined to be heterozygous for SMA (carrier status), the paternal partner was then tested; (3) if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10{\%}). The negative predictive value of DHPLC coupled with MLPA was 99.87{\%}. The combined method could detect approximately 94{\%} of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49{\%}) and SMA was diagnosed in 12 (27.91{\%}) fetuses. The prevalence of SMA in our population was 1 in 8,968. Conclusion: The main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling.",
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