An MECP2 mutation can be identified in boys, even though they do not present a Rett syndrome phenotype.

No abstract

Background-Rett syndrome is a neurodevelopmental disorder aVecting only girls; 99.5% 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. Methods-We have screened the MECP2 gene coding region for mutations in five familial cases of Rett syndrome and studied the patterns of X chromosome inactivation (XCI) in each girl. Results-We found a mutation in MECP2 in only one family. In the four families without mutation in MECP2, we found that (1) all mothers exhibit a totally skewed pattern of XCI; (2) six out of eight aVected girls also have a totally skewed pattern of XCI; and (3) it is the paternally inherited X chromosome which is active in the patients with a skewed pattern of XCI. Given that the skewing of XCI is inherited in our families, we genotyped the whole X chromosome using 32 polymorphic markers and we show that a locus potentially responsible for the skewed XCI in these families could be located on the short arm of the X chromosome. Conclusion-These data led us to propose a model for familial Rett syndrome transmission in which two traits are inherited, an X linked locus abnormally escaping X chromosome inactivation and the presence of a skewed XCI in carrier women. (J Med Genet 2001;38:435-442)

The unique LAMMER (or Clk) protein kinase of Drosophila is encoded at the Doa locus. To better understand the pleiotropic effects of Doa mutations, we describe the structure and expression of the multiple RNA and protein products of the locus, as well as their evolutionary conservation among Drosophila. The gene produces at least six different protein isoforms, primarily through alternative promoter usage, generating kinases with virtually identical catalytic domains but variable N-terminal noncatalytic domains. The single known alternative splicing event generates a kinase with the insertion of six additional amino-acids in the catalytic domain. Two independent predicted genes nested within Doa introns actually encode additional alternative N-termini of the locus. An alternative polyadenylation site utilized exclusively during early embryogenesis generates a transcript with a short half-life, apparently to ensure a "burst" of kinase expression at the onset of development. Ecdysone induction of Doa transcripts affects all isoforms during pupariation. Finally, extensive conservation of amino-acid sequences of both the catalytic and N-terminal noncatalytic exons observed in alignments between D. melanogaster exons and the genome sequences of 11 other Drosophila species suggest that the multiple isoforms serve important and nonredundant functions.

The genome of the facultative anaerobic γ-proteobacterium Shewanella oneidensis MR-1 encodes for three terminal oxidases: a bd-type quinol oxidase and two heme-copper oxidases, a A-type cytochrome c oxidase and a cbb 3-type oxidase. In this study, we used a biochemical approach and directly measured oxidase activities coupled to mass-spectrometry analysis to investigate the physiological role of the three terminal oxidases under aerobic and microaerobic conditions. Our data revealed that the cbb 3-type oxidase is the major terminal oxidase under aerobic conditions while both cbb 3-type and bd-type oxidases are involved in respiration at low-O2 tensions. On the contrary, the low O2-affinity A-type cytochrome c oxidase was not detected in our experimental conditions even under aerobic conditions and would therefore not be required for aerobic respiration in S. oneidensis MR-1. In addition, the deduced amino acid sequence suggests that the A-type cytochrome c oxidase is a ccaa 3-type oxidase since an uncommon extra-C terminal domain contains two c-type heme binding motifs. The particularity of the aerobic respiratory pathway and the physiological implication of the presence of a ccaa 3-type oxidase in S. oneidensis MR-1 are discussed.

The Darkener of apricot (Doa) locus of Drosophila encodes a LAMMER protein kinase affecting alterative splicing, and hence sex determination, via the phosphorylation of SR and SR-like proteins. Doa encodes 6 different kinases via alternative promoter usage. To provide further insight into the roles of the multiple isoforms, we mapped polymorphisms, deletions, and P-element insertions in the locus, identifying several that are largely, if not completely, isoform specific in their effects. These tests, along with the use of lines permitting overexpression and interfering RNA expression, demonstrate that the major isoforms of 55 and 105 kDa perform separate functions. The 105-kDa and a minor 138-kDa isoform are both vital but do not apparently perform functions essential for sex determination. Curiously, male-specific lethality induced by overexpression of the 55-kDa kinase in the larval fat body is rescued by coexpression of TRA, suggesting a sexspecific physiological role for this isoform. Maternal effects in which the survival of heteroallelic adults depends upon the direction of the cross are consistent with a role for a 105-kDa cytoplasmic kinase in oogenesis or early larval development.

Hydrogen metabolism plays a central role in sulfate-reducing bacteria of the Desulfovibrio genus and is based on hydrogenases that catalyze the reversible conversion of protons into dihydrogen. These metabolically versatile microorganisms possess a complex hydrogenase system composed of several enzymes of both [FeFe]-and [NiFe]-type that can vary considerably from one Desulfovibrio species to another. This review covers the molecular and physiological aspects of hydrogenases and H 2 metabolism in Desulfovibrio but focuses particularly on our model bacterium Desulfovibrio fructosovorans. The search of hydrogenase genes in more than 30 sequenced genomes provides an overview of the distribution of these enzymes in Desulfovibrio. Our discussion will consider the significance of the involvement of electron-bifurcation in H 2 metabolism.

Sulfate reducers belonging to the δ-Proteobacterial genusDesulfovibrio are ubiquitous in anoxic habitats and employ a respiratory metabolism with sulfate as the terminal electron acceptor.Molecular hydrogen plays an important role in the energy metabolism of these bacteria which can switch from respiration to fermentation. Depending on the growth conditions, H 2 can be used as the sole energy source during respiration or produced in order to oxidize reduced electron carriers to maintain the continuous conversion of the substrates during fermentation (Fauque et al., 1988;