Large-scale population carrier screening for spinal muscular atrophy in israel-effect of ethnicity on the false-negative rate

The carrier frequency of spinal muscular atrophy varies from 1:168 to 1:35. We analyzed the carrier rate in a large population in Israel, evaluated the false-negative rate based on the number of alleles with duplication of exon 7, and analyzed the ethnic differences in both parameters. Data were collected from two centers that conduct carrier screening using the multiplex ligation-dependent probe amplification kit. We studied the number of copies of exons 7 and 8 in our population, which we divided into six different ethnic groups. Statistical analysis was conducted using chi-square test. A total of 7308 healthy individuals were tested in an organized community health maintenance organization (HMO) program, and 1729 in a large hospital setup. The carrier rate was 1:62 and was not statistically different between the ethnic groups. Duplication was found in one in nine individuals (false-negative rate 5.5%) with a significant difference in frequency between the ethnic groups: 13.5% among Ashkenazim, 6% among North-African Jews (p<0.001). This difference was consistent in both centers and in exon 8 as well. There is, therefore, a higher prevalence of false negative results in some ethnic groups. The discrepancy between the rates of deletions versus duplications can be explained by the genetic disadvantage of deletions.