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

Abstract

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.

Uniparental disomy (UPD) other than 15: Phenotypes and bibliography updated

“…Maternal heterodisomy 17 due to a meiosis II nondisjunction was described in one case [Genuardi et al, 1999]. In amniocentesis trisomy 17 mosaicism was present, while only diploid cells were detected in peripheral blood after birth.…”

The Rare Regular Trisomy 17: Frequency and Phenotypic Portrait

“…However, the level of mosaicism varies greatly in different tissues and does not correlate with prognosis [11][12][13][14][15][16][17][18][19][20]. Molecular genetic analysis has confirmed mosaic T17 in several cases resulted from postzygotic mitotic errors in distribution of maternal chromosome 17 [13,16,18].…”

A novel automated strategy for screening cryptic telomeric rearrangements in children with idiopathic mental retardation

“…However, confined placental mosaicism is usually associated with intrauterine/post-natal growth retardation, a feature which was not observed in the proband. On the other hand, maternal isodisomy for chromosome 17 has previously been described in a 2-year-old boy with normal growth and psychomotor development, 19 and the terminal long arm of chromosome 17 is not known to undergo imprinting. 20 Further investigations are therefore required to know whether this region contains one or several imprinted gene(s).…”