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

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.

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy

“…Most often, SMA refers to the most common disease in this groupproximal SMA -which is further subdivided into four types based on clinical severity, as described in detail below (Engel, 2004;Wee, 2010). The incidence of SMA is between 1 in 6000 and 1 in 10,000 births (Su, 2011;Lorson, 2010;Pearn, 1978), making it the most common fatal autosomal recessive disorder (Prior, 2010).…”

Carrier screening in preconception consultation in primary care

“…Several pilot studies have been performed: in Israel with 168 pregnant and nonpregnant women (Basel-Vanagaite et al 2008); in Taiwan with 107,611 pregnant women from 383 primary clinics (Su et al 2011); and with 500 pregnant and non-pregnant women in the USA ). In the first two studies, no uptake rate was reported, whereas in the latter 60% accepted testing.…”

SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR

“…SMA is an autosomal recessive disease and is a leading genetic cause of infant death worldwide with an incidence of 1 in 6000–10,000 births (Pearn, 1978; Cuscó et al., 2002). The carrier frequency for SMA is 1:25–50 in most populations (Ben-Shachar et al., 2011; Su et al., 2011; Sugarman et al., 2012; Lyahyai et al., 2012) though it is lower for some ethnicities (Zaldívar et al., 2005; Labrum et al., 2007; Hendrickson et al., 2009; Sangaré et al., 2014). SMA results from the loss or mutation of SMN1 ( survival motor neuron 1 ; OMIM #600354) on chromosome 5q13 (Lefebvre et al., 1995).…”