Cytogenetic evaluation, fluorescence in situ hybridization, and molecular study of psu idic(X)(pter-->q22.3::q22.3-->pter) chromosome abberation in a girl with moderate growth retardation.

Combined cytogenetic, fluorescence in situ hybridization (FISH), and molecular analysis are useful in the diagnosis of sex chromosome aberrations. These methods were used in karyotype analysis of a 4-year-old girl with mild dysmorphism and growth retardation. Standard cytogenetic and FISH analysis was done on slides obtained from peripheral blood lymphocyte culture, and the molecular study was performed by using DNA polymorphism analysis. Both parents had normal karyotypes. Chromosome analysis of the proband identified the karyotype with 46 chromosomes and a late replicating dicentric X. Interphase FISH with an alpha satellite X centromere probe revealed two mosaic cell lines. Three signals were observed at 84.5% and one signal at 15.5% of the interphase cells. Molecular analysis showed that the dicentric X chromosome was of paternal origin. Based on this study, we concluded that the karyotype of the patient was 45,X/46,X, psu idic(X)(q22.3), with the trisomy Xpter-->q22.3 and monosomy Xqter-->q22.3. Dicentric X was the result of an isolocal break in both chromatids of the paternal X chromosome and subsequent rejoining of the broken ends, followed by the inactivation of one centromere. This study illustrates the usefulness of combined cytogenetic and molecular investigations for the detection of mosaicism, understanding the mechanism of the formation and parental origin of chromosomal rearrangement, and establishing the diagnosis.