Prenatal diagnosis of the derivative chromosome 22 associated with cat eye syndrome by fluorescence in situ hybridization.

Cytogenetic studies of cultured amniocytes demonstrated a karyotype of 46,XX/47,XX, +mar. A bisatellited, dicentric, distamycin-DAPI negative, NOR-positive marker was present in 76 per cent of the metaphases examined. Similar markers have been associated with cat eye syndrome (CES). We report on the utilization of fluorescence in situ hybridization (FISH) with a 14/22 alpha-satellite probe and a chromosome 22-specific cosmid for locus D22S9 to determine the origin of the prenatally detected supernumerary marker chromosome. FISH studies demonstrated that the marker is a derivative of chromosome 22 and enabled us to provide the family with additional prognostic information.

Chorionic villus sampling utilization following reports of a possible association with fetal limb defects.

Prenatal diagnosis choices were reviewed in 473 women who presented for genetic counselling prior to 11 weeks' gestation for the indication of advanced maternal age. Group A consisted of 336 patients who were unaware of a possible association between chorionic villus sampling (CVS) and limb defects. Group B consisted of 137 patients who were provided this information. Fifty-one per cent of patients in group A and 45 per cent of patients in group B chose CVS. This difference was not significant by chi 2 analysis (P = 0.7). Patterns of prenatal diagnosis procedure utilization from 1987 to 1992 revealed a significant reduction in CVS utilization accompanied by a corresponding increase in amniocentesis after the association between CVS and limb defects was publicized. Referrals for CVS counselling also significantly declined. However, acceptance rates did not change for those patients who received genetic counselling. First-trimester genetic counselling, including a discussion regarding a possible association between CVS and limb defects, helps patients make informed decisions concerning prenatal diagnosis options, and, in our population, resulted in no change in CVS acceptance rates.

Failure of PHA-stimulated i(12p) lymphocytes to divide in Pallister-Killian syndrome.

The diagnosis of Pallister-Killian syndrome (PKS) is confirmed by tissue-specific mosaicism of i(12p). The isochromosome is found in skin fibroblasts and bone marrow, but rarely in peripheral lymphocytes. The nature of the isochromosome loss was evaluated using 2 techniques: micronucleus formation for anaphase lag and in situ DNA hybridization for mosaicism in interphase cells. Cells from serial cultured fibroblasts, peripheral blood lymphocytes, and bone marrow from 4 PKS patients were used for the above analysis. Micronucleus formation was similar for PKS and normal diploid cultures, ruling out loss of i(12p) by anaphase lag as the major mechanism of in vitro mosaicism. In situ hybridization using an alpha satellite DNA probe for chromosome 12 was used to examine the presence of the i(12p) in interphase fibroblasts from 1 patient and lymphocytes from 2 patients (age 8 weeks and 1 day). The i(12p) was present in a significantly higher proportion of interphase nuclei in peripheral lymphocytes than in metaphase, suggesting the initial loss of the isochromosome is exaggerated in metaphase by selective division in vitro. In situ hybridization of peripheral lymphocyte interphase cells with chromosome 12 specific probes may be a useful supplemental procedure for the diagnosis of PKS, at least in the newborn infant.