Mapping of X chromosome inversion breakpoints [inv(X)(q11q28)] associated with FG syndrome: A second FG locus [FGS2]?

FG syndrome is an X-linked condition comprising mental retardation, congeni tal hypotonia, macrocephaly, distinctive facial changes, and constipation o r anal malformations. In a linkage analysis, we mapped a major FG syndrome locus [FGS1] to Xq13, between loci DXS135 and DXS1066. The same data, howev er, clearly demonstrated genetic heterogeneity. Recently, we studied a Fren ch family in which an inversion [inv(X)(q12q28)] segregates with clinical s ymptoms of FG syndrome. This suggests that one of the breakpoints correspon ds to a second FG syndrome locus [FGS2]. We report the results of fluoresce nce in situ hybridization analysis performed in this family using YACs and cosmids encompassing the Xq11q12 and Xq28 regions. Two YACs, one positive f or the DXS1 locus at Xq11.2 and one positive for the color vision pigment g enes and GGPD loci at Xq28, were found to cross the breakpoints, respective ly, We postulate that a gene might be disrupted by one of the breakpoints. (C) 2000 Wiley-Liss, Inc.