Eggermann Thomas
Institute of Human Genetics, University Hospital, RWTH Aachen, Germany.
Endocr Dev. 2009;14:10-9. doi: 10.1159/000207472. Epub 2009 Feb 27.
Human growth is a complex process and requires the appropriate interaction of many members. Central members in the growth axes are regulated epigenetically and thereby reflect the profound significance of imprinting for correct mammalian ontogenesis. A prominent imprinting disorder, Silver-Russell syndrome (SRS), is a congenital disease characterized by intrauterine and postnatal growth retardation and other features. SRS represents the first human disorder with imprinting dis-turbances affecting two different chromosomes: nearly one tenth of patients carry a maternal unipa-rental disomy of chromosome 7 and more than 38% show a hypomethylation in the imprinting control region 1 in 11p15. Interestingly, hypermethylation of the same region is associated with the overgrowth disease Beckwith-Wiedemann syndrome (BWS), thus SRS and BWS can be regarded as genetically (and clinically) opposite diseases. Because of the different imprinting regions involved, SRS is a suitable model to decipher the role of imprinting in growth and the functional interaction between imprinted genes in different genomic regions.
人类生长是一个复杂的过程，需要许多成员之间的适当相互作用。生长轴中的核心成员受到表观遗传调控，从而反映出印记对于正确的哺乳动物个体发育具有深远意义。一种著名的印记障碍——Silver-Russell综合征（SRS），是一种先天性疾病，其特征为宫内和出生后生长发育迟缓以及其他特征。SRS是首例因印记紊乱而影响两条不同染色体的人类疾病：近十分之一的患者携带7号染色体的母源单亲二倍体，超过38%的患者在11p15的印记控制区域1表现出低甲基化。有趣的是，同一区域的高甲基化与过度生长疾病Beckwith-Wiedemann综合征（BWS）相关，因此SRS和BWS可被视为遗传上（以及临床上）相反的疾病。由于涉及不同的印记区域，SRS是一个合适的模型，用于解读印记在生长中的作用以及不同基因组区域中印记基因之间的功能相互作用。
