Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
J Med Genet. 2022 Dec;59(12):1241-1246. doi: 10.1136/jmg-2022-108700. Epub 2022 Jul 29.
Two imprinting control centres, :IG-differentialy methylated region (DMR) and :TSS-DMR, reside on chromosome 11p15.5. Paternal deletions involving the :TSS-DMR result in variable phenotypes, namely, normal phenotype, Silver-Russel syndrome (SRS) and fetal demise. However, expression analyses for in these patients are very limited.
Patient 1 (adult woman) and patient 2 (boy in early childhood) showed prenatal and postnatal growth failure and clinical suspicion of SRS.
Both patients showed hypermethylation of the :TSS-DMR caused by the paternal heterozygous de novo deletions involving the :TSS-DMR, but not including enhancers. The deletion sizes were 5 kb and 12 kb for patients 1 and 2, respectively. gene expressions in immortalised leucocytes of both patients were increased compared with those of controls.
Paternal deletions involving the :TSS-DMR, but not including enhancers, disrupt expression, strongly activate expression and consequently cause severe growth failure.
两个印迹控制中心：IG-差异甲基化区域（DMR）和：TSS-DMR，位于 11p15.5 号染色体上。涉及：TSS-DMR 的父系缺失导致表型的可变性，即正常表型、Silver-Russel 综合征（SRS）和胎儿死亡。然而，对这些患者中的进行表达分析非常有限。
患者 1（成年女性）和患者 2（幼儿）表现出产前和产后生长发育迟缓，并伴有 SRS 的临床怀疑。
两位患者均显示：TSS-DMR 的 hypermethylation 是由父系杂合性从头缺失引起的，该缺失涉及：TSS-DMR，但不包括 enhancers。患者 1 和 2 的缺失大小分别为 5kb 和 12kb。与对照组相比，两位患者的永生白细胞中的基因表达均增加。
涉及：TSS-DMR，但不包括 enhancers 的父系缺失会破坏的表达，强烈激活的表达，从而导致严重的生长发育迟缓。
