IKBKG/NEMO gene mutations cause an X-linked, dominant neuroectodermal disorder named Incontinentia Pigmenti (IP). Located at Xq28, IKBKG/NEMO has a unique genomic organization, as it is part of a segmental duplication or low copy repeat (LCR1-LCR2, >99% identical) containing the gene and its pseudogene copy (IKBKGP). In the opposite direction and outside LCR1, IKBKG/NEMO partially overlaps G6PD, whose mutations cause a common X-linked human enzymopathy. The two LCRs in the IKBKG/NEMO locus are able to recombine through non-allelic homologous recombination producing either a pathological recurrent exon 4-10 IKBKG/NEMO deletion (IKBKGdel) or benign small copy number variations. We here report that the local high frequency of micro/macro-homologies, tandem repeats and repeat/repetitive sequences make the IKBKG/NEMO locus susceptible to novel pathological IP alterations. Indeed, we describe the first two independent instances of inter-locus gene conversion, occurring between the two LCRs, that copies the IKBKGP pseudogene variants into the functional IKBKG/NEMO, causing the de novo occurrence of p.Glu390ArgfsX61 and the IKBKGdel mutations, respectively. Subsequently, by investigating a group of 20 molecularly unsolved IP subjects using a high-density quantitative polymerase chain reaction assay, we have identified seven unique de novo deletions varying from 4.8 to ∼115 kb in length. Each deletion removes partially or completely both IKBKG/NEMO and the overlapping G6PD, thereby uncovering the first deletions disrupting the G6PD gene which were found in patients with IP. Interestingly, the 4.8 kb deletion removes the conserved bidirectional promoterB, shared by the two overlapping IKBKG/NEMO and G6PD genes, leaving intact the alternative IKBKG/NEMO unidirectional promoterA. This promoter, although active in the keratinocytes of the basal dermal layer, is down-regulated during late differentiation. Genomic analysis at the breakpoint sites indicated that other mutational forces, such as non-homologous end joining, Alu-Alu-mediated recombination and replication-based events, might enhance the vulnerability of the IP locus to produce de novo pathological IP alleles.

Oxides with proton conductivity have a great potential for applications in environmental energy technology. Despite the Ba-Ce 0.4 Zr 0.4 Y 0.2 O 3−δ (BCZY) perovskites being well-known proton conductors, it is a challenge to determine the optimal operating temperature range where the energy applications benefit most from this unique property. The protonic transport properties strongly depend on crystal structure and local distortions in the participating cation coordination sphere, according to related temperatures and gas feed. The transport and crystallographic properties of BCZY were simultaneously studied by impedance spectroscopy (IS) and synchrotron X-ray diffraction (S-XRD). A strong correlation between conductivity and the lattice parameter, corresponding in principle to a cubic symmetry, was observed, mainly between 400 and 700°C. The protonic conductivity range was analyzed by the H/D isotopic effect on the impedance spectra, which helped to identify protonic conduction as the governing transport mechanism below 600°C, while the transport via oxygen vacancies dominates above this temperature. In order to assess the real crystallographic structure, the simultaneous refinement of laboratory XRD and neutron diffraction (ND) patterns was performed. According to this, BCZY changes from rhombohedral symmetry below 400°C to cubic at 600°C in a second-order phase transition. Complementary quasielastic neutron scattering (QENS) enables us to determine a protonic jump length of 3.1 Å, which matches the O−O distances in the octahedral oxygen coordination sphere around the cations. These results support the protonic self-diffusion through proton hopping between intraoctahedral O sites as the main transport mechanism up to 600°C.

No abstract

No abstract

No abstract

No abstract

No abstract

The mechanism controlling the electrode polarization resistance response was studied for new LT-SOFC cathodes with La0.5−xPrxBa0.5CoO3−δ (0 ≤ x ≤ 0.5) compositions.