Large-scale population screening for spinal muscular atrophy: Clinical implications

  • Ben-Shachar S
  • Orr-Urtreger A
  • Bardugo E
 et al. 
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Abstract

PURPOSE 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.

Author-supplied keywords

  • MLPA
  • SMA
  • SMN1
  • carrier screening
  • spinal muscular atrophy

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Authors

  • Shay Ben-Shachar

  • Avi Orr-Urtreger

  • Eyal Bardugo

  • Ruth Shomrat

  • Yuval Yaron

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