Flori Elisabeth, Girodon Emmanuelle, Samama Brigitte, Becmeur François, Viville Brigitte, Girard-Lemaire Françoise, Doray Bérénice, Schluth Caroline, Marcellin Luc, Boehm Nelly, Goossens Michel, Pingault Véronique
Service de Cytogénétique, Fédération de Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Eur J Hum Genet. 2005 Sep;13(9):1013-8. doi: 10.1038/sj.ejhg.5201442.
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.
产前7号染色体三体通常是羊膜细胞中的细胞培养假象，出生时核型为正常二倍体，胎儿结局正常。同样，真正的产前7号染色体三体嵌合体通常会生出正常儿童，除非三体细胞在出生后持续存在，或者三体挽救导致母源单亲二体，这是导致5.5 - 7%的Silver-Russell综合征（SRS）患者患病的原因。我们在此报告一例患有母源单亲异源二体7以及肠道和皮肤成纤维细胞7号染色体三体嵌合体的患者，其SRS与先天性巨结肠症（HSCR）的不寻常关联。鉴于HSCR的发病率、多因素遗传和遗传异质性，其出现可能是偶然的。然而，肠道以及皮肤成纤维细胞中存在7号染色体三体嵌合体表明SRS和HSCR可能存在关联。这种关联可能是由于皮肤成纤维细胞（导致SRS）和肠道（导致HSCR）中的7号染色体三体嵌合体使非印记基因剂量增加，或者是通过基因组印记使皮肤成纤维细胞和肠道中母源表达的印记等位基因过表达，或者是7号染色体三体嵌合体与基因组印记共同作用的结果。本报告表明，在母源单亲二体7（mUPD(7)）患者中观察到的SRS表型也可能是由于未检测到的低水平7号染色体三体嵌合体所致。为了验证这一假设，我们建议每当出现mUPD7时，在不同组织中进行常规和分子细胞遗传学分析。
