Two unrelated patients with inversions of the X chromosome and non-specific mental retardation: physical and transcriptional mapping of their common breakpoint region in Xq13.1

Two unrelated mildly retarded males with inversions of the X chromosome and nonspecific mental retardation (MRX) are described. Case 1 has a pericentr ic inversion 46, Y,inv(X) (p11.1q13.1) and case 2 a paracentric inversion 4 6,1:inv(X) (q13.1q28). Both male patients have severe learning difficulties . The same chromosomal abnormalities were found in their mothers who are in tellectually normal. Fluorescence in situ hybridisation mapping showed a co mmon area of breakage of each of the inverted chromosomes in Xq13.1 near DX S131 and DXS162. A detailed long range restriction map of the breakpoint re gion was constructed using YAC, PAC, and cosmid clones. We show that the tw o inverted chromosomes break within a short 250 kb region. Moreover, a grou p of ESTs corresponding to an as yet uncharacterised gene was mapped to the same critical interval. We hypothesise that the common inversion breakpoin t region of the two cases in Xq13.1 may contain a new MRX gene.