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 retardation (IUGR, PNGR) and Silver-Russell syndrome (SRS [MIM 180860]). We report a case of IUGR in a newborn with SRS stigmata. Using combined haplotyping and cytogenetic-FISH studies we characterized the lymphocytes, umbilical cord and four placental cotyledons. The results are consistent with complete maternal isodisomy 7 and trisomy 7 mosaicism of post-zygotic origin. The trisomic cell line was prevalent in trophoblast cells from two placental cotyledons. Trisomy 7 of post-zygotic origin is a frequent finding, but maternal isodisomy 7, due to trisomic rescue has never been reported. PEG1/MEST expression was evaluated on placenta cDNA and a specific transcript was revealed only in the cotyledons with a high percentage of trisomic cells and the presence of the paternal chromosome 7 contribution, but not in the placental biopsies with maternal isodisomy 7. The histological features of the four placental fragments revealed that isodisomy 7 correlates with a pattern 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 cotyledons, 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 chromosome 7 in the fetus or the result of abnormal placental function during pregnancy.
Miozzo
M
M
Laboratorio di Genetica Medica, Università di Milano, Italy. monica.miozzo@unimi.it
Grati
F R
FR
Bulfamante
G
G
Rossella
F
F
Cribiù
M
M
Radaelli
T
T
Cassani
B
B
Persico
T
T
Cetin
I
I
Pardi
G
G
Simoni
G
G
D000328:Adult; D002824:Chorionic Villi / Q000648:ultrastructure; D002897:Chromosomes, Human, Pair 7; D020732:Cytogenetic Analysis; D004247:DNA / Q000032:analysis; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D015870:Gene Expression; D005865:Gestational Age; D006239:Haplotypes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics*
D011506:Proteins; C103637:mesoderm specific transcript protein; D004247:DNA