1/3. Occurrence of rett syndrome in boys.The neurologic disorder rett syndrome was originally described exclusively in girls. We present two boys with clinical features of rett syndrome. Other than head circumference deceleration, no longer considered mandatory, patient 1 meets all of the criteria. Using fluorescent in situ hybridization analysis, 97.6% of cells were found to be karyotypically normal (46,XY). No mutation was detected on screening of the coding region of the MECP2 gene. The second patient also has classic features of rett syndrome. However, cytogenetic analysis of peripheral blood revealed a karyotype 47,XXY[23]/46,XY[7] confirming mosaicism for Klinefelter's syndrome. A T158M missense mutation in the methylcytosine-binding domain of the MECP2 gene was identified. A diagnostic bias against the clinical identification of rett syndrome in boys may exist. This presentation of the male phenotype could be more common than it would appear, although boys with MECP2 mutations might also manifest in other ways. rett syndrome remains a clinical diagnosis that should not be dismissed in boys, and thorough evaluation including karyotype and mutation testing is warranted.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/3. Disruption of Netrin G1 by a balanced chromosome translocation in a girl with rett syndrome.We have identified a girl with characteristic features of rett syndrome (RTT) who carries a de novo balanced translocation involving chromosomes 1 and 7. Both breakpoints were mapped by fluorescence in situ hybridization with selected genomic clones from the regions of interest. Southern blot hybridisations, utilizing probes derived from breakpoint spanning BACs, detected several aberrant fragments specific for the patient. sequence analysis of the cloned junction fragment indicated that on chromosome 1 the predominantly brain-expressed Netrin G1 (NTNG1) gene is disrupted, whereas on chromosome 7 there was no indication for a truncated gene. The chromosome 1 breakpoint lies within the 3' part of NTNG1 and affects alternatively spliced transcripts, suggesting that the phenotype in this patient is the result of disturbed NTNG1 expression. In silico translation of the NTNG1 splice variants predicted protein isoforms with different C-termini: one membrane bound through a glycosylphosphatidylinositol anchor and the other soluble. The membrane-bound protein isoform would be affected by the breakpoint, whereas the soluble form would remain intact. Our results suggest that the central nervous system is sensitive to NTNG1 expression levels and that NTNG1 is a novel candidate disease gene for RTT.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/3. Identification and molecular characterization of a small 11q23.3 de novo duplication in a patient with rett syndrome manifestations.We report on an interstitial duplication of the long arm of chromosome 11 [46XX,dup(11) (q23.3)] in a girl with atypical rett syndrome (RS). This case was discovered during a systematic cytogenetic study of RS. Fluorescent in situ hybridization including total chromosome painting and use of regional specific YAC, cosmid and plasmid probes, was used to confirm the chromosome 11q involvement and to identify the landmarks of the smallest 11q duplication reported to date. The findings are compared to cases of trisomy 11q reported previously, all of which have a larger duplication and different clinical manifestations. Surprisingly, mental retardation and behavior disorders are less severe in these cases.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |