2 BROTHERS WITH MULTIPLE CONGENITAL-ANOMALIES AND MENTAL-RETARDATION DUE TO DISOMY (X)(Q12-]Q13.3) INHERITED FROM THE MOTHER

We present the phenotypic, cytogenetic and molecular findings in two d ysmorphic and mentally retarded brothers with disomy Xq12-->q13.3. The mother and the grandmother carry the same rearrangement of the X chro mosome, which was interpreted as an inverted insertion of the segment (X)(q12-->q13.3) into Xq21.2. The X-inactivation-specific-transcript ( XIST) is expressed in the probands' mother but is absent in her son, c onfirming the hypothesis that X inactivation is realized only if two X inactivation centers reside on different X-chromosomes (trans-configu ration). In the phenotypically normal mother the aberrant X chromosome was late replicating in all cells, indicating functional monosomy of the constitutional segment trisomy. The phenotype of the brothers is c onsidered to be the consequence of a functional disomy Xq12-->q13.3. T he trait combination observed in the brothers was compared with the sp ectrum of clinical and anthropological traits for proximal Xq disomy i n males, elaborated by phenotype analyses of the available literature cases.