Venâncio Margarida, Santos Mónica, Pereira Susana Aires, Maciel Patrícia, Saraiva Jorge M
Serviço de Genética Médica, Hospital Pediátrico de Coimbra, Coimbra, Portugal.
Eur J Hum Genet. 2007 Aug;15(8):902-4. doi: 10.1038/sj.ejhg.5201835. Epub 2007 Apr 18.
Rett syndrome (RTT; OMIM#312750) is a severe neurodevelopmental disorder that affects mainly girls. It has an estimated incidence of 1:10,000-15,000 females. Mutations in the X-linked gene methyl CpG-binding protein 2 (MECP2) have been found in most patients. The most accepted explanation for the sex bias is that the Rett mutation in sporadic cases has its origin in the paternal germline X chromosome and can thus only be transmitted to females. The majority of cases are sporadic (99.5%) but some familial cases have been described. These cases can either be explained by germline mosaicism or by asymptomatic carrier mothers with skewing of X-inactivation towards the wild-type MECP2 allele. We describe one of the few familial cases of RTT in which a maternal germline mosaicism is the most likely explanation. The mutation p.Arg270fs (c.808delC) was identified in both a girl with classical RTT and her brother who had the severe neurological phenotype usually described in males. The mutation was absent in DNA extracted from blood of both parents. These type of events must be taken into consideration in the genetic counselling of families after the diagnosis of a first case of RTT in a female or a MECP2 mutation in a male.
雷特综合征（RTT；OMIM#312750）是一种主要影响女孩的严重神经发育障碍。据估计，女性发病率为1:10,000 - 15,000。大多数患者中发现了X连锁基因甲基CpG结合蛋白2（MECP2）的突变。对这种性别偏差最被认可的解释是，散发病例中的雷特突变起源于父系生殖系X染色体，因此只能遗传给女性。大多数病例是散发性的（99.5%），但也有一些家族性病例被描述。这些病例可以用生殖系嵌合体或无症状携带者母亲的X染色体失活偏向野生型MECP2等位基因来解释。我们描述了少数几例家族性雷特综合征病例之一，其中最可能的解释是母系生殖系嵌合体。在一名患有典型雷特综合征的女孩及其患有通常在男性中描述的严重神经表型的兄弟中均发现了p.Arg270fs（c.808delC）突变。在从父母双方血液中提取的DNA中未发现该突变。在女性中诊断出首例雷特综合征病例或男性中诊断出MECP2突变后，在对家庭进行遗传咨询时必须考虑到这类事件。
