Mosaic trisomy 17 in amniocytes: phenotypic outcome, tissue distribution, and uniparental disomy studies.

Mosaicism for trisomy 17 in amniocyte cultures is a rare finding, whilst postnatal cases are exceptional. In order to gain insight into the possible effects of the distribution of the trisomic line and of uniparental disomy (UPD) on embryofoetal development, we have performed follow-up clinical, cytogenetic and molecular investigations into three newly detected prenatal cases of trisomy 17 mosaicism identified in cultured amniotic fluid. In the first case, the pregnancy ended normally with the birth of a healthy girl, and analysis of newborn lymphocytes and of multiple extra-embryonic tissues was indicative of confined placental mosaicism. The second case was also associated with a normal pregnancy outcome and postnatal development, and only euploid cells were found in peripheral blood after birth. However, maternal isodisomy 17 consequent to a meiosis II error and loss of a chromosome 17 homologue was detected in peripheral lymphocytes postnatally. In the third case, pathological examination after termination of pregnancy showed growth retardation and minor dysmorphisms, and the trisomic line was detected in foetal skin fibroblasts. In addition, biparental derivation of chromosome 17 was demonstrated in the euploid lineage. These results, together with previously reported data, indicate that true amniotic trisomy 17 mosaicism is more commonly of extra-embryonic origin and associated with normal foetal development. Phenotypic consequences may arise when the trisomic line is present in foetal tissues. Case 2 also represents the first observation of maternal UPD involving chromosome 17; the absence of phenotypic anomalies in the child suggests that chromosome 17 is not likely to be subject to imprinting in maternal gametes.

Double autosomal/gonosomal mosaic aneuploidy: study of nondisjunction in two cases with trisomy of chromosome 8.

We report cytogenetic and molecular investigations performed in two cases of mosaic trisomy 8 combined with mosaic sex chromosome aneuploidy. In a 35-year-old female, presenting with short stature, gonadal dysgenesis, and a multiple congenital anomalies/mental retardation syndrome typical of trisomy 8, chromosome analysis from peripheral lymphocytes showed the presence of three cell lines, whose karyotypes were 45,X (59.2%), 46,X,+8 (1.2%), and 47,XX,+8 (39.6%), respectively. The same cell lines were found in a skin fibroblast culture, though in different proportions. The second patient, a 9-month-old male with multiple skeletal abnormalities, showed a 47,XY,+8 and a 47,XXY cell line in both peripheral lymphocytes (61.7% and 38.3%, respectively) and skin fibroblasts (92.8% and 7.2%, respectively). To determine the events underlying the origin of these complex karyotypes we performed Southern blot and polymerase chain reaction (PCR) analysis using polymorphic DNA markers from the X chromosome and from chromosome 8. Both supernumerary chromosomes 8, and, in case 2, the two X chromosomes, appeared to be identical, lacking detectable recombination events. We conclude that, in both cases, the most likely mechanism underlying the origin of the mosaic cell lines was formation of a normal zygote, followed by mitotic errors during early divisions.

A new case of interstitial deletion of chromosome 3q, del(3q)(q13.12q21.3), with agenesis of the corpus callosum.

We describe a boy with an interstitial deletion of the proximal portion of chromosome 3q. Prominent physical characteristics were a dysmorphic face with apparent hypertelorism, signs of prenatal lymphedema, foot contractures and agenesis of the corpus callosum. The finding of corpus callosum agenesis in a previously reported patient with an overlapping deletion suggests an additional locus for this malformation.

Partial tetrasomy 9 in an infant with clinical and radiological evidence of multiple joint dislocations.

We report on an infant with partial tetrasomy of chromosome 9 due to the presence in her peripheral lymphocytes and in 55% of skin fibroblasts of an isochromosome 9 comprised of the p arm and of a portion of the q arm extending to band q21.1. The phenotype is comparable to that of other cases with a similar chromosome aberration, with multiple joint dislocations as a prominent manifestation.

Multiple "marker" chromosomes: a novel cytogenetic finding in a patient with mental retardation and congenital anomalies.

A patient with mental retardation and clinical manifestations suggestive of Noonan syndrome was found to have in her peripheral lymphocytes multiple small accessory marker chromosomes, varying in number from one to five per cell and in size from about half the size of the q arm of a G group chromosome to less than a centromere. Occasionally, in the more elongated markers, a G-positive or a C-positive band could be identified, or the marker had the appearance of a ring. The origin and significance of these marker chromosomes are discussed.