Lambert Sophie, Maystadt Isabelle, Boulanger Sébastien, Vrielynck Pascal, Destrée Anne, Lederer Damien, Moortgat Stéphanie
Department of Pediatrics, Université Catholique de Louvain (U.C.L.), Brussels, Belgium; Center for Human Genetics, Institut de Pathologie et Génétique (I.P.G.), Gosselies, Belgium.
Center for Human Genetics, Institut de Pathologie et Génétique (I.P.G.), Gosselies, Belgium; Faculty of Medicine, Université Namur (U.N.), Namur, Belgium.
Eur J Med Genet. 2016 Oct;59(10):522-5. doi: 10.1016/j.ejmg.2016.07.003. Epub 2016 Jul 25.
Mutations in MECP2 (MIM #312750), located on Xq28 and encoding a methyl CpG binding protein, are classically associated with Rett syndrome in female patients, with a lethal effect in hemizygous males. However, MECP2 mutations have already been reported in surviving males with severe neonatal-onset encephalopathy, or with X-linked intellectual disability associated with psychosis, pyramidal signs, parkinsonian features and macro-orchidism (PPM-X syndrome; MIM3 #300055). Here we report on the identification of the p.Ala140Val mutation in the MECP2 gene in 4 males and 3 females of a large Caucasian family affected with X-linked intellectual disability. Females present with mild cognitive impairment and speech difficulties. Males have moderate intellectual disability, impaired language development, friendly behavior, slowly progressive spastic paraparesis and dystonic movements of the hands. Two of them show microcephaly. The p.Ala140Val mutation is recurrent, as it was already described in 4 families with X-linked mental retardation and in three sporadic male patients with intellectual disability. We further delineate the phenotype associated with the p.Ala140Val mutation, illustrating a variable expressivity even within a given family, and we compare our patients with previous reported cases in the literature.
MECP2（MIM #312750）基因位于Xq28，编码一种甲基化CpG结合蛋白，该基因突变在女性患者中通常与瑞特综合征相关，在半合子男性中具有致死效应。然而，已有报道称，存活的男性患者中存在MECP2基因突变，这些患者患有严重的新生儿期发病的脑病，或患有与精神病、锥体束征、帕金森样特征和巨睾症相关的X连锁智力障碍（PPM-X综合征；MIM3 #300055）。在此，我们报告在一个患有X连锁智力障碍的大型高加索家族的4名男性和3名女性中鉴定出MECP2基因的p.Ala140Val突变。女性表现为轻度认知障碍和言语困难。男性有中度智力障碍、语言发育受损、行为友善、缓慢进展的痉挛性截瘫和手部肌张力障碍性运动。其中两人有小头畸形。p.Ala140Val突变具有复发性，因为它已在4个患有X连锁智力迟钝的家族以及3名患有智力障碍的散发性男性患者中被描述过。我们进一步描述了与p.Ala140Val突变相关的表型，表明即使在一个特定家族中也存在可变的表达性，并将我们的患者与文献中先前报道过的病例进行了比较。
