Jian Le, Archer Hayley L, Ravine David, Kerr Alison, de Klerk Nick, Christodoulou John, Bailey Mark E S, Laurvick Crystal, Leonard Helen
Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.
Eur J Hum Genet. 2005 Nov;13(11):1235-8. doi: 10.1038/sj.ejhg.5201479.
Among cases in the Australian Rett Syndrome Database, the nonsense mutation p.R270X is one of the most commonly occurring single pathogenic MECP2 mutations. In two recent published reports of the MECP2 mutational spectrum the p.R270X appeared to be under represented. We hypothesised that increased mortality arising from this mutation may underlie this apparent discrepancy. We investigated our hypothesis in two independent study groups from Australia and the UK with prospective data collections (total n=524). Only females with Rett syndrome and an identified MECP2 mutation were included. Significant differences in survival were detected among Rett syndrome cases grouped for the eight most frequent mutations (log-rank chi(2) (7)=15.71, P=0.03). Moreover, survival among cases with p.R270X, when compared with survival among cases with all the other mutations was reduced (log-rank chi(2) (2)=6.94, P=0.01). Our observation of a reduced survival associated with the p.R270X mutation offers an explanation for the under representation of p.R270X in older subjects with Rett syndrome.
在澳大利亚雷特综合征数据库的病例中，无义突变p.R270X是最常见的单一致病性MECP2突变之一。在最近两篇关于MECP2突变谱的报告中，p.R270X的出现频率似乎较低。我们推测，这种突变导致的死亡率增加可能是造成这种明显差异的原因。我们在来自澳大利亚和英国的两个独立研究组中进行了前瞻性数据收集，以调查我们的假设（总共n = 524）。仅纳入患有雷特综合征且已鉴定出MECP2突变的女性。在按八种最常见突变分组的雷特综合征病例中，检测到生存率存在显著差异（对数秩卡方检验(7)=15.71，P = 0.03）。此外，与所有其他突变病例的生存率相比，p.R270X突变病例的生存率降低（对数秩卡方检验(2)=6.94，P = 0.01）。我们观察到与p.R270X突变相关的生存率降低，这为p.R270X在老年雷特综合征患者中出现频率较低提供了解释。
