Laurent Villard

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..The aim of this review is to describe the nature of the MECP2 mutations identified in male patients to date and their associated phenotypes...

..They both presented with the same condition and died of severe apnea before they were 1 year old. Their sister has a classic form of Rett syndrome...

..Our results suggest that a pharmacological stimulation of the noradrenergic system could be a promising approach for the treatment of the respiratory dysfunction which causes a significant proportion of death in RS patients...

..However, an interdisciplinary approach drawing from chemistry, biology and neuroscience is needed to elucidate the mechanistic links between the genotype and phenotype of this genetic disorder...

..Finally, treating Mecp2-deficient mice with cysteamine, a molecule increasing the secretion of Bdnf vesicles, improved the lifespan and reduced motor defects, suggesting a new therapeutic strategy for Rett syndrome...

..Altogether, our findings demonstrate that Mecp2-deficiency induces nigrostriatal deficits, and they offer a new perspective to better understand the origin of motor dysfunction in RTT...

..In conclusion, our results showing a progressive catecholaminergic deficit in the LC of Mecp2 deficient null male mice could open new perspectives to better understand the autonomic and cognitive deficits due to the lack of Mecp2...

..Extensive screening in the mentally retarded population will be needed to determine if ATP8A2 haploinsufficiency or dysfunction causes a neurological phenotype in humans...

..Our data suggest that FER is not implicated in the mental retardation phenotype observed in the reported patient. Therefore the MR phenotype might not be caused by the translocation...

..In conclusion, our results offer new insights to better understand the mechanisms leading to autonomic dysfunction in RS...

..Subsequently, motor functions and respiratory metabolism are severally impaired. A detailed description of these gradual defects may help to identify their neuronal origin and to elaborate novel therapeutic strategies...

..These findings clearly call for a careful consideration of the pathogenicity of the MECP2 mutations identified in sporadic male cases before genetic counselling or prenatal diagnosis is proposed to the corresponding families...

..5% of Rett syndrome cases are sporadic, although several familial cases have been reported. Mutations in the MECP2 gene were identified in approximately 70-80% of sporadic Rett syndrome cases...

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..A significant proportion of these malformations could have a genetic basis. However, genetic studies are limited because most cases are sporadic and mendelian forms are rare...

..However, we were not able to correlate the developmental expression of MeCP2 in a given area of the brainstem with autonomic dysfunctions occurring in the presence of a mutation in Mecp2...

..Among the different morbid phenotypes assigned to the region, X-linked mental retardation would be the best candidate to be associated with this gene...

..It suggests that mutations will be predominantly found in the helicase region as well as in the zinc finger regions and leads us to propose a large screening of additional patients...

..These data indicate that xnp-1 and XNP/ATR-X have diverged from the same ancestral DNA helicase gene and may therefore have conserved similar functions at the cellular level...

..To refine the phenotype associated with STXBP1 aberrations in early onset epileptic syndromes, we studied this gene in a cohort of patients with early onset epileptic encephalopathy...

..The association of PMG with the disruption of its transcript suggests that, in addition to its recently uncovered function in the immune system, the NHEJ1 protein may also play a role during development of the human cerebral cortex...

..Given our current knowledge and the tools available, modulating biogenic amine metabolism may prove to be the most promising strategy for improving the life quality of Rett syndrome patients in the short term...

..After P3, the expression of Kiaa2022 decreases and maintains very low levels thereafter. Our results show that Kiaa2022 is expressed in the developing brain and that it may play a role in postmitotic, maturing neurons...

..These data indicate that TBX22 may be the first identified member of a new family of T-domain-containing proteins...

..We found a specific interaction between the XNP and the EZH2 proteins. In light of these observations, we discuss how the XNP protein may regulate gene transcription at the chromatin level...

..In this paper, we report a mutation in XNP, segregating in a family presenting an "ATR-X' phenotype without alpha-thalassemia, that causes a proline to serine transition in the helicase II domain...

..Furthermore, we uncovered an important reduction of brain ATP level, a hitherto undetected anomaly of energy metabolism that may reflect and contribute to cerebral injury and dysfunction...

..Linkage of XMEA to the Xq28 region is thus firmly established. In addition, we have ruled out the Emery-Dreifuss muscular dystrophy to be allelic with XMEA by direct sequencing of the emerin gene in three of our families...

..This approach is simple, does not require RNA preparation, does not involve time consuming mutation detection methods, and can thus be applied to a large number of patients at a low cost in any given laboratory...

..In addition, affected males display facial similarities that can help the diagnosis. Most carrier females have mild mental retardation and subtle facial changes...

..This transcriptional map incorporates 51 transcription units and provides a useful resource of candidate genes for some of the disorders assigned to this region of the X chromosome...

..Mutation screening of probands from 20 unrelated XLMR families linked to the proximal short arm of the human X chromosome failed to show any mutation in the coding region of the KLF8 gene...

..These data demonstrate the high allelic heterogeneity of RTT in France and provide information relevant to the development of strategies for molecular diagnosis and genetic counseling in RTT families...

..Given that this is a minimum incidence because complete inventory was not possible, this study of patients with Rett syndrome reinforces the fact that the great majority of patients with Rett syndrome have a MECP2 mutation...

..We hypothesize that breathing disturbances in Mecp2-/y mice, and probably Rett patients, originate in part from a deficiency in noradrenergic and serotonergic modulation of the medullary respiratory network...

..We conclude that expression of TBX22 is entirely consistent with the CPX phenotype and that the mouse should provide a useful model for elucidating its role in craniofacial development...