Characterization of a chromosome 8-derived minute marker chromosome using microdissection and FISH in a boy with growth retardation.

In a 9-year-old boy referred because of growth retardation, chromosome analysis showed the presence of a minute marker chromosome in 75% of the metaphases examined. The application of microdissection in combination with fluorescence in situ hybridization demonstrated that the marker was derived from the centromere region of chromosome 8, the karyotype being: mos 47,XY,+mar.ish der(8)(D8Z1+)[75]/46,XY[25]. The clinical and cytogenetical findings are compared with cases previously reported in the literature.

ICF syndrome: a new case and review of the literature.

Patients with ICF syndrome can be recognized by the presence of a variable immunodeficiency, instability of the pericentromeric heterochromatin of, in particular, chromosomes 1, 9, and 16 in cultured peripheral lymphocytes, and a number of facial anomalies. Recently, aberrations at the molecular level have been described, consisting of alterations in the methylation pattern of classical satellite DNA, in a number of patients. ICF syndrome is considered to be inherited in an autosomal recessive manner and may be rare, as only 14 patients have been described thus far. We present a new case, a boy with agammaglobulinemia, who was extensively studied by means of classical cytogenetics and fluorescent in situ hybridization. All patients previously reported in the literature are reviewed.

Distribution of meiotic recombination along nondisjunction chromosomes 21 in Down syndrome determined using cytogenetics and RFLP haplotyping.

Ten families (Down syndrome children and their parents) showing evidence of meiotic recombination between intraparental chromosomes transmitted after nondisjunction were studied. Cytogenetic polymorphisms and a cassette of RFLP markers distributed along chromosome 21 were used to analyze these families to localize the regions of meiotic recombination. Results indicated that only one crossover occurred per meiotic division and that nine of ten nondisjunctions appeared to be of maternal origin. In one family the crossover had taken place in the pericentromeric region, proximal to marker D21S13, which is quite exceptional. A chance of meiotic recombination within region 21q21, flanked by marker D21S72 and the amyloid gene, could be demonstrated in seven of the ten families. Most strikingly, this chance significantly decreased distal to q21, with frequencies of 0.3 and 0.1 in regions q22.2 and q22.3-qter, respectively. It is hypothesized that decreased chiasmata formation in the most distal part of chromosome 21q might promote nondisjunction. Furthermore, data from the ten crossovers made it possible to map provisionally two previously undefined markers, D21S24 and D21S82, to regions q21-qter and q22.1-qter, respectively.

On the origin of recurrent trisomy 21: determination using chromosomal and DNA polymorphisms.

A family is described in which two cases of trisomy 21 occurred in, respectively, a newborn infant and a prenatally diagnosed fetus. Using fluorescent chromosomal polymorphisms, it was established that in both cases the extra chromosome resulted from a first meiotic division error in the mother and that the father contributed the same centromeric region to both children. RFLP-associated probes were used to examine the genetic content of the chromosomes. It was noted that the polymorphism patterns of the chromosomes 21 which both children inherited from their parents were identical for three, but not identical for one of the probes studied. This difference must be the result of recombination. This result is discussed in relation to the suggestion that the increased recurrence rate in mothers with a trisomic child could be due to a reduced recombination rate.