A Gene for FG Syndrome Maps in the Xq12-q21.31 Region Sylvain Briault, 1 * Ruth Hill, 2 Antony Shrimpton, 3 Danping Zhu, 4 Marianne Till, 5 Nathalie Ronce, 1 Patricia Margaritte-Jeannin, 6 Michael Baraitser, 2 Helen Middleton-Price, 2 Sue Malcolm, 2 Elizabeth Thompson, 2 Joe Hoo, 3 Golder Wilson, 7 Corrado Romano, 8 Agne ` s Guichet, 1 Marcus Pembrey, 2 Michel Fontes, 9 Annemarie Poustka, 10 and Claude Moraine 1 1 Service de Ge ´ne ´tique, CHU Bretonneau, Tours, France 2 Institute of Child Health, University of London, London, England 3 SUNY Health Science Center, Syracuse, New York 4 The Wilmer Eye Institute, Baltimore, Maryland 5 Service de Ge ´ne ´tique, Ho ˆpital Debrousse, Lyon, France 6 INSERM U155, Chateau de Longchamp, Paris, France 7 Southwestern Medical Center, Dallas, Texas 8 Department of Pediatrics, Associazione Oasi Maria SS, Troina, Italy 9 INSERM U406, Faculte ´ de Me ´decine, Marseille, France 10 Deutsches Krebsforschungszentrum, Heidelberg, Germany FG syndrome is an X-linked recessive condi- tion in which mental retardation is associ- ated with congenital hypotonia, macro- cephaly, characteristic face, and constipa- tion. This syndrome was mapped by Zhu et al. [Cytogenet Cell Genet 1991;58:2091A] to Xq21.31-q22 by linkage analysis with a max lod score of 1.2 for the DXYS1X, DXS178, DXS101, and DXS94 loci and crossovers at DXS16 (Xp22.31) and DXS287 (Xq22.3). How- ever, this mapping was only provisional and needed to be refined. In this paper, we re- port the results of a new linkage analysis performed on 10 families including that studied by Zhu et al. [1991]. Two-point analysis demonstrated linkage with DXS441 (Zmax = 3.39 at  = 0.12) at Xq13. In addition, separate analysis of the lod scores obtained for the Xq13 markers suggested linkage ex- clusion for three families. Genetic heteroge- neity was confirmed by analysis of the link- age results with the HOMOG program (max logL = 4.07,  = 0,  = 0.65). Localization of one FG gene between DXS135 and DXS1066 was suggested by analysis of crossovers found in those three families which were as- sumed to be linked to Xq13 with a probabil- ity of 0.95 or more. This region could be re- duced to the DXS135-DXS72 interval after combining our data with those from dele- tions previously described in males in the Xq13-q21 region. Am. J. Med. Genet. 73:87– 90, 1997. © 1997 Wiley-Liss, Inc. KEY WORDS: FG syndrome; linkage; X chromosome; genetic hetero- geneity INTRODUCTION FG syndrome (MIM 305450), first described by Opitz and Kaveggia [1974], is an X-linked recessive condition in which severe to mild mental retardation is associ- ated with reduced fetal movements, congenital hypoto- nia, severe chronic constipation with or without anal anomalies (imperforate or anteriorly placed anus, anal stenosis, or skin tags), relative macrocephaly, and an unusual personality [Opitz et al., 1988]. In most pa- tients, the facial traits are not striking and could be largely due to the hypotonic open-mouthed appearance [Thompson et al., 1985] and to macrocephaly. They in- clude a broad and tall forehead, hypertelorism and/or telecanthus, downslanting palpebral fissures, multiple hair whorls, and cowlicks of the frontal hairline. The syndrome is variable and the physical findings, except for anal stenosis, are, in general, nonspecific, making the diagnosis difficult. This has led to speculation that the condition is likely to be heterogeneous [Thompson et al., 1989]. In the first linkage study, performed by Zhu et al. [1991] in the family described by Keller et al. [1976], a Contract grant sponsor: Association Franc ¸aise contre les Myo- pathies; Contract grant sponsor: Groupement de Recherches et d’Etudes des Genomes; Contract grant sponsor: Hendricks Fund for Medical Research. *Correspondence to: Sylvain Briault, Service de Ge ´ne ´tique, CHU Bretonneau, 2 bl Tonnelle ´, 37044 Tours Cedex, France. E-mail: Briault@med.univ-tours.fr Received 23 January 1997; Accepted 28 April 1997 American Journal of Medical Genetics 73:87–90 (1997) © 1997 Wiley-Liss, Inc.