Department of Neurology, Drammen Hospital, Vestre Viken Hospital Trust, P.O. Box 800, 3004 Drammen, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, P.O. Box 1171, Blindern 0318, Oslo, Norway.
Department of Habilitation, Innlandet Hospital Trust, Anders Sandvigs v. 17, 2629 Lillehammer, Norway; Department of Psychology, University of Oslo, P.O. Box 1094, Blindern 0317, Oslo, Norway.
Brain Dev. 2020 Aug;42(7):484-495. doi: 10.1016/j.braindev.2020.03.008. Epub 2020 Apr 23.
Rett syndrome (RTT) is a neurodevelopmental disorder mainly caused by mutations in MECP2. The diagnostic criteria of RTT are clinical; mutations in MECP2 are neither diagnostic nor necessary, and a mutation in another gene does not exclude RTT. We attempted to correlate genotype and phenotype to see if there are significant clinical associations.
All available females diagnosed with RTT in Norway were invited to the study. Parents were interviewed, the girl or woman with RTT examined and medical records reviewed. All diagnoses were revisited according to the current diagnostic criteria and exome-based sequencing analyses were performed in individuals without an identified causative mutation. Participants were categorized according to genotypes and RTT diagnosis. Individuals with RTT with and without mutations in MECP2 were compared.
Ninety-one individuals were included. A presumed causative mutation was identified in 86 individuals, of these, mutations in MECP2 in 77 individuals and mutations in SMC1A, SYNGAP1, SCN1A, CDKL5, FOXG1 or chromosome 13q in nine. Seventy-two individuals fulfilled the diagnostic criteria for classic and 12 for atypical RTT. Significant differences in early development, loss of hand use and language, intense eye gaze and the presence of early onset epilepsy were revealed in individuals with RTT according to their MECP2 genotypic status.
Using the current diagnostic criteria, genetic and clinical variation in RTT is considerable. Significant differences between individuals with RTT with and without MECP2 mutations indicate that MECP2 is a major determinant for the clinical phenotype in individuals with RTT.
雷特综合征（RTT）是一种主要由 MECP2 基因突变引起的神经发育障碍。RTT 的诊断标准是临床标准；MECP2 基因突变既不是诊断标准，也不是必要条件，另一个基因的突变也不能排除 RTT。我们试图将基因型与表型相关联，以观察是否存在显著的临床关联。
挪威所有被诊断为 RTT 的女性均被邀请参加该研究。对其父母进行访谈，对患有 RTT 的女孩或女性进行检查，并查阅病历。根据当前的诊断标准重新检查所有诊断，并对未发现致病突变的个体进行外显子组测序分析。根据基因型和 RTT 诊断对参与者进行分类。比较 MECP2 基因突变和无突变的 RTT 患者。
共纳入 91 例患者。86 例患者中发现了一种假定的致病突变，其中 77 例为 MECP2 基因突变，9 例为 SMC1A、SYNGAP1、SCN1A、CDKL5、FOXG1 或 13q 染色体突变。72 例符合经典 RTT 诊断标准，12 例符合非典型 RTT 诊断标准。根据 MECP2 基因型状态，具有 RTT 的个体在早期发育、丧失手功能和语言能力、强烈的眼神注视以及早期发作性癫痫方面存在显著差异。
使用当前的诊断标准，RTT 的遗传和临床变异性相当大。具有和不具有 MECP2 基因突变的 RTT 个体之间的显著差异表明，MECP2 是 RTT 个体临床表型的主要决定因素。
