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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Graduate Institute of Clinical Genomics, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Hung
authors.forename: Shin-Yu
authors.initials: SY
authors.lastname: Lin
authors.forename: Fang-Yi
authors.initials: FY
authors.lastname: Chen
authors.forename: Jimmy P S
authors.initials: JP
authors.lastname: Chern
authors.forename: Chris
authors.initials: C
authors.lastname: Tsai
authors.forename: Tai-Sheng
authors.initials: TS
authors.lastname: Chang
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Yang
authors.forename: Hung
authors.initials: H
authors.lastname: Li
authors.forename: Hong-Nerng
authors.initials: HN
authors.lastname: Ho
authors.forename: Chien-Nan
authors.initials: CN
authors.lastname: Lee
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D005820:Genetic Testing; D005828:Genetics, Population; D006579:Heterozygote; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics*; D011237:Predictive Value of Tests; D011247:Pregnancy; D037841:Pregnant People; D011296:Prenatal Diagnosis / Q000379:methods; D011446:Prospective Studies; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics; D013997:Time Factors; D055815:Young Adult
chemical_list: C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein