title: Trisomy 7 mosaicism, maternal uniparental heterodisomy 7 and Hirschsprung's disease in a child with Silver-Russell syndrome.
abstract: Prenatal trisomy 7 is usually a cell culture artifact in amniocytes with normal diploid karyotype at birth and normal fetal outcome. In the same way, true prenatal trisomy 7 mosaicism usually results in a normal child except when trisomic cells persist after birth or when trisomy rescue leads to maternal uniparental disomy, which is responsible for 5.5-7% of patients with Silver-Russell syndrome (SRS). We report here on the unusual association of SRS and Hirschsprung's disease (HSCR) in a patient with maternal uniparental heterodisomy 7 and trisomy 7 mosaicism in intestine and skin fibroblasts. HSCR may be fortuitous given its frequency, multifactorial inheritance and genetic heterogeneity. However, the presence of the trisomy 7 mosaicism in intestine as well as in skin fibroblasts suggests that SRS and HSCR might possibly be related. Such an association might result from either an increased dosage of a nonimprinted gene due to trisomy 7 mosaicism in skin fibroblasts (leading to SRS) and in intestine (leading to HSCR), or from an overexpression, through genomic imprinting, of maternally expressed imprinted allele(s) in skin fibroblasts and intestine or from a combination of trisomy 7 mosaicism and genomic imprinting. This report suggests that the SRS phenotype observed in maternal uniparental disomy 7 (mUPD(7)) patients might also result from an undetected low level of trisomy 7 mosaicism. In order to validate this hypothesis, we propose to perform a conventional and molecular cytogenetic analysis in different tissues every time mUPD7 is displayed.
authors.affiliation: Service de Cytogénétique, Fédération de Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Elisabeth.Flori@chru-strasbourg.fr
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Flori
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Girodon
authors.forename: Brigitte
authors.initials: B
authors.lastname: Samama
authors.forename: François
authors.initials: F
authors.lastname: Becmeur
authors.forename: Brigitte
authors.initials: B
authors.lastname: Viville
authors.forename: Françoise
authors.initials: F
authors.lastname: Girard-Lemaire
authors.forename: Bérénice
authors.initials: B
authors.lastname: Doray
authors.forename: Caroline
authors.initials: C
authors.lastname: Schluth
authors.forename: Luc
authors.initials: L
authors.lastname: Marcellin
authors.forename: Nelly
authors.initials: N
authors.lastname: Boehm
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Véronique
authors.initials: V
authors.lastname: Pingault
mesh_terms: D000328:Adult; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7; D005145:Face / Q000002:abnormalities; D005260:Female; D006130:Growth Disorders / Q000235:genetics*; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009030:Mosaicism; D011247:Pregnancy; D011296:Prenatal Diagnosis; D013577:Syndrome; D014314:Trisomy; D024182:Uniparental Disomy