Carrier Screening for Spinal Muscular Atrophy (SMA) in 107,611 Pregnant Women during the Period 2005–2009: A Prospective Population-Based Cohort Study

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

doi:10.1371/journal.pone.0017067

Abstract

BackgroundSpinal 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 FindingsThis 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.ConclusionThe 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.

Highlights

The main purpose of carrier screening is to identify asymptomatic carrier couples with no family history who are at risk for offspring with a specific genetic disease
The main benefit of Spinal muscular atrophy (SMA) carrier screening is to reduce the burden associated with giving birth to an affected child
The American College of Medical Genetics recommended routine carrier screening for spinal muscular atrophy (SMA) in the general population because of its high carrier frequency and the severity of the genetic disease [1]

Summary

Introduction

The main purpose of carrier screening is to identify asymptomatic carrier couples with no family history who are at risk for offspring with a specific genetic disease. The American College of Medical Genetics recommended routine carrier screening for spinal muscular atrophy (SMA) in the general population because of its high carrier frequency and the severity of the genetic disease [1]. Proximal SMA is the most common autosomal recessive neurodegenerative disorder. This severe neuromuscular disease affects 1 in 5,000 to 1 in 10,000 live births and is associated with an overall carrier frequency of 1 in 35 to 1 in 50 in the general population [2,3,4,5]. 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

Results

Conclusion