Folkhälsan Institute of Genetics, Helsinki, and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
Department of Dermatology, Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Sci Rep. 2017 Nov 16;7(1):15693. doi: 10.1038/s41598-017-16070-5.
Silver-Russell syndrome (SRS) is a growth retardation syndrome in which loss of methylation on chromosome 11p15 (11p15 LOM) and maternal uniparental disomy for chromosome 7 [UPD(7)mat] explain 20-60% and 10% of the syndrome, respectively. To search for a molecular cause for the remaining SRS cases, and to find a possible common epigenetic change, we studied DNA methylation pattern of more than 450 000 CpG sites in 44 SRS patients. Common to all three SRS subgroups, we found a hypomethylated region at the promoter region of HOXA4 in 55% of the patients. We then tested 39 patients with severe growth restriction of unknown etiology, and found hypomethylation of HOXA4 in 44% of the patients. Finally, we found that methylation at multiple CpG sites in the HOXA4 promoter region was associated with height in a cohort of 227 healthy children, suggesting that HOXA4 may play a role in regulating human growth by epigenetic mechanisms.
银-罗素综合征（SRS）是一种生长发育迟缓综合征，其中 11p15 号染色体上的甲基化缺失（11p15 LOM）和 7 号染色体上的母源单亲二体性（UPD(7)mat）分别解释了 20-60%和 10%的综合征。为了寻找剩余 SRS 病例的分子病因，并发现可能存在的共同表观遗传变化，我们研究了 44 名 SRS 患者中超过 450000 个 CpG 位点的 DNA 甲基化模式。我们发现，在所有三个 SRS 亚组中，有 55%的患者在 HOXA4 的启动子区域存在低甲基化区域。然后，我们测试了 39 名病因不明的严重生长受限的患者，发现其中 44%的患者存在 HOXA4 低甲基化。最后，我们发现 HOXA4 启动子区域多个 CpG 位点的甲基化与 227 名健康儿童的身高有关，提示 HOXA4 可能通过表观遗传机制在调节人类生长中发挥作用。
