Cytogenetic and Molecular Genetic Characterization of Trisomy 20 Mosaicism in Fetal Blood and Tissues

Abstract

We report a case of mosaic trisomy 20, the most common autosomal mosaicism identified in amniocytes, ascertained in a woman referred for amniocentesis because of abnormal ultrasound at 18·1 weeks' gestation which revealed short femurs and nuchal thickening. Metaphase analysis of 98 clones revealed 47,XY,+20 in 96 cells (98 per cent). Trisomy 20 was demonstrated in 6 cells (12 per cent) in a total of 50 cells from two fetal blood cultures obtained after pregnancy termination. Fluorescence in situ hybridization (FISH) analysis of interphase nuclei utilizing a chromosome 20 alpha‐satellite centromeric DNA probe revealed three signals in 57/546 nuclei (10 per cent) in fetal blood. Metaphase analysis of 167 cells from seven different fetal tissue sources revealed trisomy 20 in 32 cells (19·2 per cent). The percentage of trisomy 20 cells varied with tissue type, with the highest percentage (13/25 cells, 52 per cent) identified in the small intestine and lymph nodes and the lowest percentage (1/34 cells, 2·9 per cent) identified in a specimen of chorionic villi. Molecular genetic analyses utilizing polymerase chain reaction (PCR)‐formated dinucleotide repeat polymorphisms demonstrated that the non‐disjunctional event most likely occurred post‐zygotically and that the origin of the extra chromosome 20 was maternal. This study is the first to demonstrate trisomy 20 cells in fetal blood, suggesting that mosaic trisomy 20 can be embryonic in origin. In cases of prenatally detected mosaic trisomy 20, examination of fetal blood should be considered, as well as study of placental membranes, skin, and urine sediment to confirm the karyotype and determine its significance.

Maternal uniparental isodisomy 20 in a foetus with trisomy 20 mosaicism: clinical, cytogenetic and molecular analysis

“…8 In that case, 10 dinucleotide repeat polymorphisms spaced along the short and long arms of chromosome 20 failed to reveal three different alleles in the proband DNA, and as no recombination was observed between markers, the findings suggested that the nondisjunction event most likely occurred postzygotically. 8 Biparental inheritance was detected in the diploid chorionic villi.…”

“…8 In that case, 10 dinucleotide repeat polymorphisms spaced along the short and long arms of chromosome 20 failed to reveal three different alleles in the proband DNA, and as no recombination was observed between markers, the findings suggested that the nondisjunction event most likely occurred postzygotically. 8 Biparental inheritance was detected in the diploid chorionic villi. 8 The fact that 78% of the reported prenatal cases of trisomy 20 mosaicism were diagnosed after an amniocentesis because of advanced maternal age, however, suggests a maternal age effect (and maternal meiotic origin in the majority of cases) as seen in other trisomies, ie 13, 16, 18, 21, and X.…”

“…8 Biparental inheritance was detected in the diploid chorionic villi. 8 The fact that 78% of the reported prenatal cases of trisomy 20 mosaicism were diagnosed after an amniocentesis because of advanced maternal age, however, suggests a maternal age effect (and maternal meiotic origin in the majority of cases) as seen in other trisomies, ie 13, 16, 18, 21, and X. 2,25 A molecular study of seven spontaneous abortions with nonmosaic trisomy 20 showed meiotic origin in five cases (three maternal and two undetermined) and probable somatic origin in two cases.…”

“…6 The origin of the extra chromosome 20 has been investigated in one case of an aborted foetus, where generalised trisomy 20 mosaicism was present in different foetal as well as placental tissues, and where the extra chromosome 20 originated from a maternal meiosis II or postzygotic mitotic nondisjunction. 8 Infants with a normal karyotype from a pregnancy in which a mosaic trisomy cell line was found in amniocytes or trophoblastic cells, are potentially at risk for uniparental disomy (UPD). 9 There are five reports in the literature of UPD20 (one of which was confined to 20q) and abnormal phenotypic findings (Table 1).…”