title: Large-scale population screening for spinal muscular atrophy: clinical implications.
abstract: OBJECTIVE
  To determine the frequency of SMN1 deletion carriers in the Israeli population and to assess the feasibility of population screening for spinal muscular atrophy.
  
  
  METHODS
  A total of 6394 individuals without family history of spinal muscular atrophy underwent genetic screening by multiplex ligation-dependent probe amplification, designed to detect SMN1 exon 7 and exon 8 copy number.
  
  
  RESULTS
  One hundred fifty-nine individuals carried an SMN1 heterozygous exon 7 deletion, yielding a carrier frequency of 1:40. About 10.8% of individuals were found to carry two or more SMN1 exon 7 copies on the same chromosome (cis configuration). This implies that some deletion carriers may not be detected by multiplex ligation-dependent probe amplification or similar quantitative methods. The acceptance of spinal muscular atrophy screening among women undergoing testing for fragile X syndrome and cystic fibrosis reached 93%.
  
  
  CONCLUSIONS
  Currently used molecular techniques cannot detect about 5% of spinal muscular atrophy carriers with a cis configuration or individuals with SMN1 sequence mutations and de novo deletions. Thus, it is estimated that the spinal muscular atrophy carrier detection rate is about 90%. Given the severity of spinal muscular atrophy, the relatively high carrier frequency, and the estimated detection rate, we conclude that population-based screening for spinal muscular atrophy is feasible and acceptable.
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Ben-Shachar
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
authors.forename: Eyal
authors.initials: E
authors.lastname: Bardugo
authors.forename: Ruth
authors.initials: R
authors.lastname: Shomrat
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yaron
mesh_terms: D056915:DNA Copy Number Variations; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007557:Israel / Q000453:epidemiology; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D017384:Sequence Deletion; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
chemical_list: C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein