Post-zygotic origin of complete maternal chromosome 7 isodisomy and consequent loss of placental PEG1/MEST expression

Maternal UPD of chromosome 7 is associated with pre- and postnatal growth r etardation (IUGR, PNGR) and Silver-Russell syndrome (SRS [MIM 180860]). We report a case of IUGR in a newborn with SRS stigmata. Using combined haplot yping and cytogenetic-FISH studies we characterized the lymphocytes, umbili cal cord and four placental cotyledons. The results are consistent with com plete maternal isodisomy 7 and trisomy 7 mosaicism of post-zygotic origin. The trisomic cell line was prevalent in trophoblast cells from two placenta l cotyledons. Trisomy 7 of post-zygotic origin is a frequent finding, but m aternal isodisomy 7, due to trisomic rescue has never been reported. PEG1/M EST expression was evaluated on placenta cDNA and a specific transcript was revealed only in the cotyledons with a high percentage of trisomic cells a nd the presence of the paternal chromosome 7 contribution, but not in the p lacental biopsies with maternal isodisomy 7. The histological features of t he four placental fragments revealed that isodisomy 7 correlates with a pat tern of cotyledonary hyper-ramification due to an increase of the branching angiogenesis, which could be the result of a defect of angiogenesis caused by the absence of PEG1 product. The severe hypo-ramification of the two co tyledons, showing trisomy 7 mosaicism, may be due to the triplicate dosage of genes on chromosome 7. The delayed fetal growth could be the phenotypic effect of the imbalance between imprinted and non-imprinted genes on chromo some 7 in the fetus or the result of abnormal placental function during pre gnancy. (C) 2001 Harcourt Publishers Ltd.