Molecular cloning of Xp11 breakpoints in two unrelated mentally retarded females with X;autosome translocations

Mental retardation is a very common and extremely heterogeneous disorder th at affects about 3% of the human population. Its molecular basis is largely unknown, but many loci have been mapped to the X chromosome. We report on two mentally retarded females with X;autosome translocations and breakpoint s in Xp11, viz., t(X;17)(pll;p13) and t(X;20)(pll;q13). (Fiber-) FISH analy sis assigned the breakpoints to different subbands, Xp11.4 and Xp11.23, sep arated by approximately 8 Mb. High-resolution mapping of the X-chromosome b reakpoints using Southern blot hybridization resulted in the isolation of b reakpoint-spanning genomic subclones of 3 kb and 0.5 kb. The Xp11.4 breakpo int is contained within a single copy sequence, whereas the Xp11.23 breakpo int sequence resembles an L1 repetitive element. Several expressed sequence s map close to the breakpoints, but none was found to be inactivated. There fore, mechanisms other than disruption of X-chromosome genes likely cause t he phenotypes. Copyright (C) 2000 S. Karger AG, Basel.