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.
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.
Authors: Silvina Noemi Contreras-Capetillo; Hugo Leonid Gallardo Blanco; Ricardo Martin Cerda-Flores; José Lugo-Trampe; Iris Torres-Muñoz; Antonio Bravo-Oro; Carmen Esmer; Laura Ella Martínez DE Villarreal Journal: Exp Ther Med Date: 2015-04-20 Impact factor: 2.447
Authors: Deborah L Stabley; Ashlee W Harris; Jennifer Holbrook; Nicholas J Chubbs; Kevin W Lozo; Thomas O Crawford; Kathryn J Swoboda; Vicky L Funanage; Wenlan Wang; William Mackenzie; Mena Scavina; Katia Sol-Church; Matthew E R Butchbach Journal: Mol Genet Genomic Med Date: 2015-03-21 Impact factor: 2.183
Authors: Miho Maeda; Ashlee W Harris; Brewster F Kingham; Casey J Lumpkin; Lynn M Opdenaker; Suzanne M McCahan; Wenlan Wang; Matthew E R Butchbach Journal: PLoS One Date: 2014-09-05 Impact factor: 3.240