RESUMEN
Photoparoxysmal response (PPR) is considered to be a risk factor for idiopathic generalised epilepsy (IGE) and it has a strong genetic basis. Two genome-wide linkage studies have been published before and they identified loci for PPR at 6p21, 7q32, 13q13, 13q31 and 16p13. Here we combine these studies, augmented with additional families, in a mega-analysis of 100 families. Non-parametric linkage analysis identified three suggestive peaks for photosensitivity, two of which are novel (5q35.3 and 8q21.13) and one has been found before (16p13.3). We found no evidence for linkage at four previously detected loci (6p21, 7q32, 13q13 and 13q31). Our results suggest that the different family data sets are not linked to a shared locus. Detailed analysis showed that the peak at 16p13 was mainly supported by a single subset of families, while the peaks at 5q35 and 8q21 had weak support from multiple subsets. Family studies clearly support the role of PPR as a risk factor for IGE. This mega-analysis shows that distinct loci seem to be linked to subsets of PPR-positive families that may differ in subtle clinical phenotypes or geographic origin. Further linkage studies of PPR should therefore include in-depth phenotyping to make appropriate subsets and increase genetic homogeneity.
Asunto(s)
Epilepsia Refleja/genética , Ligamiento Genético/genética , Genoma Humano/genética , Mapeo Cromosómico/métodos , Cromosomas Humanos Par 16/genética , Cromosomas Humanos Par 5/genética , Cromosomas Humanos Par 8/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , MasculinoRESUMEN
PURPOSE: Quantitative trait loci (QTL) mapping in mice revealed a seizure-related QTL (Szs1), for which the inward-rectifying potassium channel Kcnj10 is the most compelling candidate gene. Association analysis of the human KCNJ10 gene identified a common KCNJ10 missense variation (Arg271Cys) that influences susceptibility to focal and generalized epilepsies. The present replication study tested the initial finding that the KCNJ10 Cys271 allele is associated with seizure resistance to common syndromes of idiopathic generalized epilepsy (IGE). METHODS: The study sample comprised 563 German IGE patients and 660 healthy population controls. To search for seizure type-specific effects, two IGE subgroups were formed, comprising 258 IGE patients with typical absences (IAE group) and 218 patients with juvenile myoclonic epilepsy (JME group). A TaqMan nuclease assay was used to genotype the KCNJ10 single nucleotide polymorphism c.1037C > T (dbSNP: rs1130183) that alters amino acid at position 271 from arginine to cysteine. RESULTS: Replication analysis revealed a significant decrease of the Cys271 allele frequency in 446 IGE patients compared to controls (chi2 = 3.52, d.f. = 1, P = 0.030, one-sided; OR(Cys271+) = 0.69; 95% CI: 0.50-0.95). Among the IGE subgroups, lack of the Cys271 allele was accentuated in the JME group (chi2 = 5.20, d.f. = 1, P = 0.011, one-sided). CONCLUSION: Our results support previous evidence that the common KCNJ10 Arg271Cys missense variation influences seizure susceptibility of common IGE syndromes.
Asunto(s)
Alelos , Epilepsia Generalizada/genética , Predisposición Genética a la Enfermedad , Canales de Potasio de Rectificación Interna/genética , Arginina/genética , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Cisteína/genética , Análisis Mutacional de ADN/métodos , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Mutación Missense , Polimorfismo GenéticoRESUMEN
A complete description of the 4sigma photoionization dynamics of NO has been derived from angle resolved photoelectron-photoion-coincidence experiments. The combination of measurements performed with linearly and circularly polarized light has made it possible to obtain a unique set of complex dipole matrix elements. A comparison with multichannel-Schwinger-configuration-interaction calculations shows good agreement in the general shapes of the angular distributions due to the correct description of the main components and phase differences. Still, many transition moments agree only qualitatively.
RESUMEN
The two-dimensional electronic band structure of monolayer Bi on GaP(110) has been mapped using angle-resolved UV photoelectron spectroscopy (ARUPS) with synchrotron radiation. Surface photovoltage effects are corrected for by simultaneous second-order core spectroscopy. From valence-band spectra along the four symmetry directions of the surface Brillouin zone at three photon energies it is possible to distinguish three states as surface related. The topmost band is found to be inside the fundamental band gap, at ca 0.75 eV above the bulk valence-band maximum. Comparison with other V/III-V(110) systems shows that this system is not significantly different, despite the relatively large size of the Bi atoms with respect to the GaP lattice; in a selective comparison with InP and GaAs it would appear that Bi-substrate anion bonding is a more important factor than strain.
