Department of Medical Genetics, University of Athens School of Medicine, Choremio Research Laboratory, Aghia Sophia Children's Hospital, Athens 11527, Greece.
Pediatr Res. 2010 May;67(5):551-6. doi: 10.1203/PDR.0b013e3181d4ecf7.
The MECP2 gene mutations cause Rett syndrome (RTT) (OMIM: 312750), an X-linked dominant disorder primarily affecting girls. Until RTT was considered lethal in males, although now approximately 60 cases have been reported. Males with MECP2 mutations present with a broad spectrum of phenotypes ranging from neonatal encephalopathy to nonsyndromic mental retardation (MR). Four boys (aged, 3-11 y) were evaluated for MR. Patient 1 had autistic features. Patients 2 and 3 were brothers both presenting with psychomotor delay. Patient 4 showed dysmorphic features and behavioral problems reminiscent of FXS. All patients had a normal 46, XY karyotype and three were tested for FXS with negative results. MECP2 gene analysis of exons 3 and 4 was performed using methods based on the PCR, including Enzymatic Cleavage Mismatched Analysis (ECMA) and direct sequencing. Patient 1 presented somatic mosaicism for the classic RTT p.R106W mutation and patient 4 carried the p.T203M polymorphism. Analysis of the mothers in both cases revealed normal DNA sequences. Patients 2 and 3 had a novel deletion (c.1140del86) inherited from their unaffected mother. MECP2 gene mutations may be considered a rare cause of MR in males although great phenotypic variation hinders genotype-phenotype correlation.
MECP2 基因突变导致雷特综合征（RTT）（OMIM：312750），这是一种主要影响女孩的 X 连锁显性疾病。直到 RTT 被认为在男性中是致命的，尽管现在已经报告了大约 60 例病例。男性 MECP2 突变表现出广泛的表型范围，从新生儿脑病到非综合征性智力障碍（MR）。有 4 名男孩（年龄 3-11 岁）因 MR 接受评估。患者 1 有自闭症特征。患者 2 和 3 是兄弟俩，均表现为精神运动发育迟缓。患者 4 表现出类似于 FXS 的发育不良特征和行为问题。所有患者均具有正常的 46,XY 核型，其中 3 人进行了 FXS 检测，结果均为阴性。使用基于 PCR 的方法，包括酶切错配分析（ECMA）和直接测序，对 Exons 3 和 4 的 MECP2 基因进行了分析。患者 1 存在经典 RTT p.R106W 突变的体细胞嵌合体，患者 4 携带 p.T203M 多态性。对两位患者的母亲进行分析发现，其 DNA 序列正常。患者 2 和 3 从其未受影响的母亲那里遗传了一种新的缺失（c.1140del86）。MECP2 基因突变可能被认为是男性智力障碍的罕见原因，尽管表型变异很大，阻碍了基因型-表型相关性。
