Characterisation ofan inverted X chromosome (pl1.2q21.3) associated withmental retardation using FISH

We reportonapatient withapericentric inversionof the X chromosome, 46,Y,inv(X)(p11.2q21.3), whowasreferred forcytogenetic analysis becauseofmild mentalretardation, shortstature, prepubescentmacro-orchidism, and submucouscleft palate. Thesamechromosomal abnormality wasfoundintheproband's mother.Theinverted X chromosomewas latereplicating inallthemother's lymphocytesstudied, indicative ofa likely unbalanced inversion. We show,byfluorescencein situhybridisation (FISH) usinga paneloforderedyeastartificial chromosome(YAC)clones, thattheXp breakpoint islocalised inXpl1.23between DXS146 and DXS255and thattheXq breakpoint isassigned totheX-Yhomologousregion inXq21.3. YACscrossing the Xp andXq breakpoints havebeenidentified. Oneofthesetwobreakpoints could belinked tothementalretardation inthis patient asmany non-specific mentalretardation (MRX)loci havepreviously been located inthepericentromeric regionof theX chromosome. Morever, theelucidationatthemolecular levelofthisrearrangementwillalsoindicate ifcleft palate or prepubescent macro-orchidism, or both,inthisboyarerelated tooneofthe twoX breakpoints. (7Med Genet 1998;35:146-150)