Large deletions of the MECP2 gene detected by gene dosage analysis in patients with Rett syndrome

The original article to which this Erratum refers was published in Human Mutation 23:234–244 Human Mutation(2004) 23(3) 234–244     

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.      

A study of the effects of vigabatrin on the central nervous system and retina of Sprague Dawley and Lister-Hooded rats

Vigabatrin (gamma-vinyl GABA), an enzyme-activated, irreversible inhibitor of GABA transaminase, was administered orally to albino Sprague Dawley and pigmented Lister-Hooded rats. A dose-dependent retinal lesion characterized histologically by disruption of the outer nuclear layer was observed in the Sprague Dawley rat but not in Lister-Hooded rats, indicating that this alteration is related to the absence of pigment. The lesion is similar to that induced in albino rats by light and certain drugs. In addition, myelin vacuolation of the brain was observed in both rat strains, consistent with the findings of other toxicity studies with vigabatrin. In all cases, the vacuolation was limited to myelinated tracts and resulted from separation of the myelin sheath at the intraperiod line. There was no evidence of demyelination, axonal degeneration or damage to contiguous structures in the affected areas. The vacuolation is histologically similar to that induced in rats by certain other compounds such as isoniazid, hexachlorophene, and triethyltin, but differs in that it is focal in distribution, it is limited to the brain, and is reversible upon cessation of treatment.