American Journal of zyxw Medical Genetics zyx 30:355-368 (1988) Prenatal Diagnosis of Fragile X Syndrome by Placental (Chorionic Villi) Biopsy Culture Mark J. McKinley, Lyndal U. Kearney, Kypros H. Nicolaides, Christine M. Gosden, Tessa P. Webb, and Jean P. Fryns zyx Harris Birthright Research Centre for Fetal Medicine, London (M. J. M., L.U.K., K.H. N.); MRC Clinical and Population Genetics Unit, Edinburgh, Scotland (C.M.G.); Department of Clinical Genetics, Birmingham Maternity Hospital, Edgbaston, England (T. P. W.); and Division of Human Genetics, Universitaire Zickenheuzen Leuven, Leuven, Belgium (J. P. F.) zyx Second trimester ultrasound-guided fetal blood sampling and placental biopsy were performed on 10 pregnancies at risk for fra(X)-linked mental retardation (Martin-Bell syndrome). Three cases were diagnosed as affected after cytogenetic analysis of fetal blood and placental cultures. The fra(X)(q27.3) and common fragile sites were shown to be expressed at a lower level in placenta than in fetal blood. Induction methods included methotrexate, 5-fluore2-deoxyuridine, and excess thymidine. Excess thymi- dine may give the best expression of fra(X)(q27.3). Enhancement of fra(X)(q27.3) expression was not shown with caffeine or 5-methoxybenzamide. Key words: fragile X, fragile sites, prenatal diagnosis, fetal blood, placental biopsy, caffeine INTRODUCTION The Martin-Bell (fragile X) syndrome is attributed to a gene linked to a fragile site at band Xq27.3 [Krawczun et al., 1985; FRAXA, Berger et a]., 1985; McKusick, 19861.It is the second most common cytogenetic disorder contributing to mental handicap, after trisomy 21 [Sutherland and Hecht, 19851. Because of the severity, frequency [Opitz, 1986, 19871, and X-linked mode of inheritance [Weaver and Sherman, 19871, there is a great need for a reliable routine method for prenatal diagnosis of this syndrome [Lancet Editorial, 19861 zyxwvut . Received for publication March 9,1987; revision zyxwvu received October 1, 1987. Address reprint requests to Mark .I. McKinley, Regional Cytogenetics Unit, St. Mary’s Hospital, Whitworth Park, Manchester, M13 OJH, United Kingdom. zyxwv 0 1988 Alan R. Liss, Inc.