We conducted a prospective intervention study of screening for fragile X syndrome in the general population. Antenatal and preconceptional screening were carried out in 9459 women aged between 19 and 44 with no known family history of fragile X syndrome. 80% were tested antenatally. 134 carriers were detected (a frequency of 1 in 70); 130 had a premutation (PM) and 4 had a full mutation (FM). Prenatal diagnosis was carried out in 108 concurrent or subsequent pregnancies among carriers involving 111 fetuses. Nine had an FM, a rate of 1 in 12; two of the affected embryos received the FM directly from the mother and in seven it was the result of expansion from a PM. In all cases with an FM the pregnancy was terminated. In PM carriers there was evidence of a selection against the mutated chromosome with a segregation ratio of 0.40. Owing to the high rate of premutated chromosomes in our population we conclude that screening for fragile X syndrome among women of reproductive age should be more widely available. Copyright © 2000 John Wiley & Sons, Ltd.

Several studies on small homogenous populations suggested that fragile-X syndrome originated from a limited number of founder chromosomes. The Israeli Jewish population could serve as an adequate model for tracing a founder effect due to the unique ethnic makeup and traditional lifestyle. Furthermore, a common haplotype for Jewish Tunisian fragile X patients was recently reported. To test for a similar occurrence in the Jewish Ashkenazi population, we performed haplotype analysis of 23 fragile-X patients and 28 normal chromosomes, all Jewish Ashkenazi, using microsatellite markers within and flanking the FMR-1 gene: FRAXAC1, FRAXAC2, and DXS548. The combined triple-marker analysis identified a wide range of diverse haplotypes in patients and controls, with no distinct haplotype prevalent in the patient group. Our data suggest that no common ancestral X chromosome is associated with the fragile-X syndrome in the Israeli Jewish Ashkenazi patient population studied. These findings are in contrast to other reports on founder effect associated with fragile-X syndrome in distinct European as well as Jewish Tunisian populations. On this basis, a more complex mechanism for the development of fragile-X syndrome in the Jewish Ashkenazi population should be considered.

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.

No abstract