Objective

To present a cohort of 8 males and perform a systematic review of all published cases with a single copy of MECP2 carrying a pathogenic variant.

Methods

We reviewed medical records of males with a single copy of MECP2 carrying a pathogenic variant. We searched in Medline (Pubmed) and Embase to collect all articles which included well-characterized males with a single copy of MECP2 carrying a pathogenic or likely pathogenic variant in MECP2 (1999–2020).

Results

The literature search yielded a total of 3,185 publications, of which 58 were included in our systematic review. We were able to collect information on 27 published patients with severe neonatal encephalopathy, 47 individuals with isolated or familial mental retardation X-linked 13 (XLMR13), as well as 24 individuals with isolated or familial Pyramidal signs, parkinsonism, and macroorchidism (PPM-X).

In our cohort, we met eight individuals aged 4 to 19-year-old at the last evaluation. Three MECP2-associated phenotypes were seen in male carriers of a single copy of the gene: severe neonatal encephalopathy (n = 5); X-linked intellectual deficiency 13 (n = 2); and pyramidal signs, parkinsonism, and macroorchidism (PPM-X) (n = 1). Two novel de novo variants [p.(Gly252Argfs∗7) and p.(Tyr132Cys)] were detected.

Conclusion

In males, the MECP2 pathogenic variants can be associated with different phenotypes, including neonatal severe encephalopathy, intellectual deficiency, or late-onset parkinsonism and spasticity. The typical RS phenotype is not expected in males, except in those with Klinefelter syndrome or somatic mosaicism for MECP2.

中文翻译：

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男性 MECP2 相关疾病：系统文献回顾和另外 8 例病例

客观的

展示一组 8 名男性，并对所有已发表的病例进行系统评价，其中包含一个携带致病变异的MECP2副本。

方法

我们审查了携带致病性变异的单份MECP2男性的医疗记录。我们在 Medline (Pubmed) 和 Embase 中进行了搜索，以收集所有文章，其中包括具有良好特征的男性，这些男性具有 MECP2 的单个副本，在MECP2 (1999-2020)中携带致病性或可能的致病性变异。

结果

文献检索共产生 3,185 篇出版物，其中 58 篇被纳入我们的系统评价。我们能够收集有关 27 名已发表的严重新生儿脑病患者、47 名患有孤立性或家族性智力迟钝 X 连锁 13 (XLMR13) 的患者以及 24 名患有孤立性或家族性锥体征、帕金森症和大睾丸症( PPM- X）。

在我们的队列中，我们在最后一次评估中遇到了 8 名 4 至 19 岁的人。在单拷贝基因的男性携带者中观察到三种MECP2相关表型：严重新生儿脑病（n = 5）；X连锁智力缺陷13（n = 2）；和锥体征、帕金森症和大睾丸症 (PPM-X) (n = 1)。检测到两个新的从头变体 [p.(Gly252Argfs∗7) 和 p.(Tyr132Cys)]。

结论

在男性中，MECP2致病变异可能与不同的表型相关，包括新生儿严重脑病、智力缺陷或迟发性帕金森症和痉挛。预计男性不会出现典型的 RS 表型，除了那些患有 Klinefelter 综合征或MECP2的体细胞嵌合体的患者。