Griscelli syndrome-type 2 in twin siblings: case report and update on RAB27A human mutations and gene structure

Griscelli syndrome (GS) is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1, Elejalde), RAB27A (GS2) or MLPH (GS3) genes. Typical features of all three subtypes of this disease include pigmentary dilution of the hair and skin and silvery-gray hair. Whereas the GS3 phenotype is restricted to the pigmentation dysfunction, GS1 patients also show primary neurological impairment and GS2 patients have severe immunological deficiencies that lead to recurrent infections and hemophagocytic syndrome. We report here the diagnosis of GS2 in 3-year-old twin siblings, with silvery-gray hair, immunodeficiency, hepatosplenomegaly and secondary severe neurological symptoms that culminated in multiple organ failure and death. Light microscopy examination of the hair showed large, irregular clumps of pigments characteristic of GS. A homozygous nonsense mutation, C-T transition (c.550C>T), in the coding region of the RAB27A gene, which leads to a premature stop codon and prediction of a truncated protein (R184X), was found. In patient mononuclear cells, RAB27A mRNA levels were the same as in cells from the parents, but no protein was detected. In addition to the case report, we also present an updated summary on the exon/intron organization of the human RAB27A gene, a literature review of GS2 cases, and a complete list of the human mutations currently reported in this gene. Finally, we propose a flow chart to guide the early diagnosis of the GS subtypes and Chédiak-Higashi syndrome.FAPESPCNPq(FAEPA) Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão PretoCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Stimulated CO Dissociation and Surface Graphitization by Microfocused X-ray and Electron Beams

The irradiation with photons or electrons can dramatically influence the chemical stability of a molecule, either free or adsorbed on a surface, inducing its fragmentation or desorption. We revisit here the exostimulated dissociation of CO, a prototypical case, choosing hcp thin cobalt films as model support. Intense, microfocused soft X-rays or electron beams are used to locally stimulate CO dissociation. Fast-XPS gives direct access to the adsorbates' chemical state and coverage during irradiation, enabling the kinetics of the process to be monitored in real time. The energy-dependent cross sections for photon and electron stimulated molecular dissociation and desorption are estimated for a fixed initial CO coverage of 1/3 ML. In the soft X-ray regime, the desorption channel always prevails over dissociation and is significantly enhanced above the O K edge. The relative dissociation probability increases steadily with increasing photon energy, reaching 30% at 780 eV. Furthermore, we show that low energy electrons in the range 50 to 200 eV dissociate CO more efficiently than X-rays. The prolonged irradiation of the Co surface in CO ambient is found to produce a continuous increase of the carbon coverage, initially promoting the formation of carbides and subsequently accumulating sp2 carbon on the surface. Far from being a detrimental effect, the CO stimulated dissociation can be exploited to lithographically graft carbon-rich microscopic patterns on Co, with resolution well into the nanometer scale. A brief thermal treatment following irradiation results in the formation of a graphitic carbon overlayer, which effectively protects Co from oxidation upon exposure to ambient conditions, preserving its out-of-plane magnetic anisotropy and domain configuration

Magnetic Patterning by Electron Beam-Assisted Carbon Lithography

We report on the proof of principle of a scalable method for writing the magnetic state by electron-stimulated molecular dissociative adsorption on ultrathin Co on Re(0001). Intense microfocused low-energy electron beams are used to promote the formation of surface carbides and graphitic carbon through the fragmentation of carbon monoxide. Upon annealing at the CO desorption temperature, carbon persists in the irradiated areas, whereas the clean surface is recovered elsewhere, giving origin to chemical patterns with nanometer-sharp edges. The accumulation of carbon is found to induce an in-plane to out-of-plane spin reorientation transition in Co, manifested by the appearance of striped magnetic domains. Irradiation at doses in excess of 1000 L of CO followed by ultrahigh vacuum annealing at 380 \ub0C determines the formation of a graphitic overlayer in the irradiated areas, under which Co exhibits out-of-plane magnetic anisotropy. Domains with opposite magnetization are separated here by chiral Ne\ue9l walls. Our fabrication protocol adds lateral control to spin reorientation transitions, permitting to tune the magnetic anisotropy within arbitrary regions of mesoscopic size. We envisage applications in the nano-engineering of graphene-spaced stacks exhibiting the desired magnetic state and properties