Screening for fragile X syndrome in women of reproductive age

We conducted a prospective intervention study of screening for fragile X sy ndrome in the general population. Antenatal and preconceptional screening w ere carried out in 9459 women aged between 19 and 44 with no known family h istory of fragile X syndrome. 80% were tested antenatally. 134 carriers wer e detected (a frequency of 1 in 70); 130 had a premutation (Phl) 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 directl y 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 wa s 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 pop ulation we conclude that screening for fragile X syndrome among women of re productive age should be more widely available. Copyright (C) 2000 John Wil ey & Sons, Ltd.