Nectoux Juliette, Girard Benoit, Bahi-Buisson Nadia, Prieur Fabienne, Afenjar Alexandra, Rosas-Vargas Haydee, Chelly Jamel, Bienvenu Thierry
Assistance Publique-Hopitaux de Paris, Laboratoire de Biochimie et Génétique Moléculaires, Hôpital Cochin, France.
Pediatr Neurol. 2007 Oct;37(4):270-4. doi: 10.1016/j.pediatrneurol.2007.06.002.
Mutations in the methyl-cytosine-phosphate-guanosine dinucleotide (CpG) binding protein 2 gene are identified in up to 90% of patients with classic Rett syndrome. However, the lack of methyl-CpG binding protein 2 mutations in a small group of classic Rett syndrome cases, and the low frequency of these mutations in atypical Rett syndrome patients, suggest that other gene defects may play a role in this disorder. One report described a patient with atypical Rett syndrome who presented with early epilepsy and a de novo translocation which disrupted the Netrin G1 gene. This study tested a sample of 91 female patients with a clinically heterogeneous phenotype ranging from encephalopathy with epilepsy to atypical Rett syndrome without epilepsy for mutations in the Netrin G1 gene, to evaluate its involvement in this condition. Nine sequence variations (including six novel variations) were identified, all of which were unlikely to be pathogenic. One was a novel C to G transversion, resulting in a p.Leu537Val amino-acid substitution in one patient. The same substitution was detected in the asymptomatic mother, suggesting an absence of biological significance. Our study suggests that Netrin G1 is not involved in atypical Rett syndrome or in unexplained encephalopathy with epilepsy, but in specific forms to be delineated better in the future.
在高达90%的典型雷特综合征患者中可发现甲基胞嘧啶-磷酸-鸟嘌呤二核苷酸（CpG）结合蛋白2基因的突变。然而，一小部分典型雷特综合征病例中缺乏甲基CpG结合蛋白2突变，且这些突变在非典型雷特综合征患者中的发生率较低，这表明其他基因缺陷可能在该疾病中起作用。一份报告描述了一名患有非典型雷特综合征的患者，该患者出现早期癫痫，并有一个破坏Netrin G1基因的新生易位。本研究检测了91名女性患者的样本，这些患者具有从伴有癫痫的脑病到无癫痫的非典型雷特综合征等临床异质性表型，以检测Netrin G1基因中的突变，以评估其在这种疾病中的作用。共鉴定出9种序列变异（包括6种新变异），所有这些变异都不太可能是致病性的。其中一种是新的C到G颠换，导致一名患者出现p.Leu537Val氨基酸替代。在无症状的母亲中也检测到了相同的替代，这表明其没有生物学意义。我们的研究表明，Netrin G1不参与非典型雷特综合征或不明原因的伴有癫痫的脑病，但在未来有待更明确界定的特定形式中可能有关。
