Fragile Xq27.3infemale heterozygotes forthe Martin-Bell syndrome

X inactivation studies havebeencarried outon lymphocytes fromeight unrelated females heterozygous fortheMartin-Bell syndrome. Fourofthese carriers wereofnormal IQandfourwerementally handicapped. WhenBrdUwasusedtodifferentiate between theactive andinactive X chromosome an average of55%offra(X) wereactive intheretarded subjects, butonly27%wereactive inthoseof normalIQ.When 3H thymidine was usedto differentiate between theactive andinactive X chromosome, anaverage of58%ofmitoses from handicapped subjects and33%ofmitoses from normal subjects showed anactive fra(X) ininformative cells. Theseresults arecompared with previously published studies anditisconcluded thatthe numberofinactive fra(X) chromosomes calculated asaproportion ofallcells scored isthesamein mentally normalandmentally retarded subjects. However, thenumberofactive fra(X) chromosomesisconsistently higher intheretarded thanin thenormal females. Someofthemanyintriguing aspects ofthecytogenetics andinheritance patterns showninfamilies withthefragile X syndrome arethose associated with female carriers. Onethird offemale heterozygotes are ofimpaired mental ability andnearly always have detectable levels ofthefragile X,while approximately onethird ofthecarriers with anormal IQdonotshow themarker withanyculture methodcurrently available. 12Asageneral rule those carrier females whoare ofimpaired mental ability also showhigher levels of fragile X thandonormal carriers, although, aswith