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A 10-year-old African-American male has been followed since 2 years of age due to his mental retardation, severe behavioral problems, and dysmorphism. Conventional cytogenetic analysis, chromosome painting, high-resolution comparative genomic hybridization (HR-CGH), and bacterial artificial chromosome fluorescent in situ hybridization (BAC FISH) revealed an apparent duplication in the short arm of a chromosome 11, dup(11)(p14.3p15.1), seen also in his mentally retarded mother. The proband had moderate to severe mental retardation, a history of IUGR, infantile hypotonia, FTT, exotropia, inguinal hernia repair, and several dysmorphic features. His mother had mild mental retardation, a history of impulsivity, assaultive outbursts, and similar dysmorphism. Although G-banding and FISH indicated a duplication, HR-CGH confined the localization of material to bands 11p14-11p15 and aided the selection of locus-specific BAC clones to more precisely characterize the duplicated region. To our knowledge, the results represent the first example of a familial, cytogenetically visible duplication of euchromatin in 11p that excludes the Beckwith-Wiedemann syndrome critical region. It is possible that one or more genes had been disrupted at the breakpoints of the above structural chromosomal rearrangement giving rise to the present phenotype.

Rapid fluorescence in situ hybridization (FISH) performed on 1,788 amniocenteses, using Aneuvision (Vysis) probes for chromosomes 13, 18, 21, X, and Y, over several years, yielded 115 cases with percentages of aneuploidy between 4 and 100%. All cases above 60% were confirmed to be positive by chromosome analysis. Fifteen of forty-one cases that would be considered inconclusive by generally accepted criteria (i.e. with less than 60% of cells with an abnormal signal pattern) revealed lower cutoffs to be positive when confirmed by chromosome analysis. For trisomy 21, 6 cases with percentages from 36 to 57% were positive; 4 of 7 cases with percentages from 22.5 to 33% were positive; 11 cases with percentages of 13% or less were negative. Similar trends were found for aneuploidies of 13, 18, X, and Y. However, the number of abnormal cases is still too small to determine definitive cutoffs in the <60% gray zone. An average of 57 metaphases was analyzed for cases with FISH percentages below 60%. Despite the wide range of abnormal FISH percentages for chromosomally positive cases, we found no examples of autosomal mosaicism in this series. Although sex chromosome mosaicism was cytogenetically evident in several cases, there was little direct correlation between cytogenetic and rapid FISH results. FISH results involving sex chromosomes were more frequently confounded by maternal cell contamination and other technical factors., ((c) 2006 S. Karger AG, Basel)

We report a recurrent partial monosomy of 18p10-->11.2 and proximal partial trisomy of 18q10-->21.3 caused by a maternal pericentric inversion of chromosome 18, involving breakpoints p11.2 and q21q21.3 Based on cytogenetics and FISH analysis, we speculate that the recurrent chromosome abnormality in the proband and in the fetus was the result of a translocation, possibly in a germ cell or germ cell precursor, between the maternal normal 18 and her inverted 18, resulting in maternal germinal mosaicism, i.e. 46,XX,inv(18)/46,XX,t[18;inv(18)][q10;q10]. The unbalanced karyotype of the proband and the fetus is 46,XY,+18,der[18;inv(18)][q10;q10]. To the best of our knowledge, there are no reports of this combination of proximal 18p monosomy and proximal 18q trisomy. The other interesting observation was association of Hirschsprung's disease in the proband.

Disease associated balanced chromosome rearrangements (DBCR) causing truncation, deletion, inactivation or over-expression of specific genes are instrumental in identifying and cloning several disease genes and are estimated to be much more common than anticipated. In one survey, the minimal frequency of combined balanced de novo reciprocal translocations and inversions causing abnormal phenotype is estimated to be 0.17%, a sixfold increase compared to the general population suggesting a causative linkage between the abnormality and the observed phenotypic traits. Here, we report two new cases of apparently balanced de novo translocations resulting in developmental delay and dysmorphic features.