Sharp A, Moore G, Eggermann T
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wilts., SP2 8BJ, UK.
Eur J Hum Genet. 2001 Dec;9(12):887-91. doi: 10.1038/sj.ejhg.5200740.
The finding of maternal uniparental disomy for chromosome 7 (matUPD7) in approximately 7% of Silver-Russell syndrome (SRS) cases has lead to the assumption that imprinted gene(s) on chromosome 7 are responsible for at least some cases. However, the observation in a familial case that both maternal and paternal inheritance of proximal 7p results in an SRS-like phenotype suggests that the causative genes may not be imprinted, and that an extra copy of genes within this region cause SRS. As all cases of complete matUPD7 could have arisen by trisomy rescue, it is possible that undetected trisomy 7 mosaicism contributes towards the phenotype of SRS, and that the matUPD7 seen in some cases is a consequence of trisomy rescue. Previous studies in cases of trisomy rescue for a number of autosomes have shown a strong association with skewed X inactivation in diploid tissues. Thus, we hypothesised that if trisomy mosaicism was involved in SRS, the frequency of skewed X inactivation should be increased in a population of non-matUPD7 SRS patients. Consistent with this hypothesis, results showed a significant increase in the frequency of completely skewed X inactivation in SRS patients (three of 29) when compared to controls (three of 270), suggesting the possible presence of undetected trisomy 7 in SRS patients and/or their placentas.
在约7%的Silver-Russell综合征（SRS）病例中发现了母源7号染色体单亲二倍体（matUPD7），这使得人们推测7号染色体上的印迹基因至少导致了部分病例的发生。然而，在一个家族病例中观察到，7号染色体短臂近端的母源和父源遗传均导致了类似SRS的表型，这表明致病基因可能不是印迹基因，并且该区域内基因的额外拷贝会导致SRS。由于所有完全matUPD7的病例可能都是通过三体挽救产生的，所以未检测到的7号染色体三体嵌合体可能对SRS的表型有影响，并且在某些病例中看到的matUPD7是三体挽救的结果。先前对一些常染色体三体挽救病例的研究表明，其与二倍体组织中X染色体失活偏斜有很强的关联。因此，我们推测，如果三体嵌合体参与了SRS的发生，那么在非matUPD7的SRS患者群体中，X染色体失活偏斜的频率应该会增加。与这一推测一致的是，结果显示，与对照组（270例中有3例）相比，SRS患者（29例中有3例）中完全偏斜的X染色体失活频率显著增加，这表明SRS患者及其胎盘可能存在未检测到的7号染色体三体。
