SMALL MARKER X-CHROMOSOMES LACK THE X-INACTIVATION CENTER - IMPLICATIONS FOR KARYOTYPE PHENOTYPE CORRELATIONS/

The abnormal phenotype and/or mental retardation seen in persons with small marker X (mar(X)) chromosomes has been hypothesized to be due to the loss of the X inactivation center (XIC) at Xq13.2, resulting in t wo active copies of genes in the pericentromeric region. In order to d efine precisely the DNA content of mar(X) chromosomes and to correlate phenotype with karyotype, we studied small mar(X) chromosomes, using FISH with probes in the juxtacentromeric region. One of the probes was a 40-kb genomic cosmid for the XIST gene, which maps to the smallest interval known to contain the XIC and is thought to be involved in X i nactivation. Our findings reveal that small mar(X) chromosomes do not include the XIC and therfore cannot be subject to X inactivation, supp orting the premise that abnormal dosage of expressed genes in the peri centromeric region of the X generates the aberrant phenotype seen in p atients with small mar(X) chromosomes.