1,860 research outputs found
Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss
BACKGROUND: Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. OBJECTIVES: To describe the genotypic and clinical spectrum of biallelic KITLG-variants. METHODS: We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. RESULTS: We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. CONCLUSIONS: We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism
Novel Machado-Joseph disease-modifying genes and pathways identified by whole-exome sequencing
Machado-Joseph disease (MJD/SCA3) is a neurodegenerative polyglutamine disorder exhibiting a wide spectrum of phenotypes. The abnormal size of the (CAG)n at ATXN3 explains ~55% of the age at onset variance, suggesting the involvement of other factors, namely genetic modifiers, whose identification remains limited. Our aim was to find novel genetic modifiers, analyse their epistatic effects and identify disease-modifying pathways contributing to MJD variable expressivity. We performed whole-exome sequencing in a discovery sample of four age at onset concordant and four discordant first-degree relative pairs of Azorean patients, to identify candidate variants which genotypes differed for each discordant pair but were shared in each concordant pair. Variants identified by this approach were then tested in an independent multi-origin cohort of 282 MJD patients. Whole-exome sequencing identified 233 candidate variants, from which 82 variants in 53 genes were prioritized for downstream analysis. Eighteen disease-modifying pathways were identified; two of the most enriched pathways were relevant for the nervous system, namely the neuregulin signaling and the agrin interactions at neuromuscular junction. Variants at PARD3, NFKB1, CHD5, ACTG1, CFAP57, DLGAP2, ITGB1, DIDO1 and CERS4 modulate age at onset in MJD, with those identified in CFAP57, ACTG1 and DIDO1 showing consistent effects across cohorts of different geographical origins. Network analyses of the nine novel MJD modifiers highlighted several important molecular interactions, including genes/proteins previously related with MJD pathogenesis, namely between ACTG1/APOE and VCP/ITGB1. We describe novel pathways, modifiers, and their interaction partners, providing a broad molecular portrait of age at onset modulation to be further exploited as new disease-modifying targets for MJD and related diseases
Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance
This paper presents DELPHI measurements and interpretations of
cross-sections, forward-backward asymmetries, and angular distributions, for
the e+e- -> ffbar process for centre-of-mass energies above the Z resonance,
from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are
consistent with the predictions of the Standard Model and are used to study a
variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering
and several models which include physics beyond the Standard Model: the
exchange of Z' bosons, contact interactions between fermions, the exchange of
gravitons in large extra dimensions and the exchange of sneutrino in R-parity
violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.
A Determination of the Centre-of-Mass Energy at LEP2 using Radiative 2-fermion Events
Using e+e- -> mu+mu-(gamma) and e+e- -> qqbar(gamma) events radiative to the
Z pole, DELPHI has determined the centre-of-mass energy, sqrt{s}, using energy
and momentum constraint methods. The results are expressed as deviations from
the nominal LEP centre-of-mass energy, measured using other techniques. The
results are found to be compatible with the LEP Energy Working Group estimates
for a combination of the 1997 to 2000 data sets.Comment: 20 pages, 6 figures, Accepted by Eur. Phys. J.
Study of Tau-pair Production in Photon-Photon Collisions at LEP and Limits on the Anomalous Electromagnetic Moments of the Tau Lepton
Tau-pair production in the process e+e- -> e+e-tau+tau- was studied using
data collected by the DELPHI experiment at LEP2 during the years 1997 - 2000.
The corresponding integrated luminosity is 650 pb^{-1}. The values of the
cross-section obtained are found to be in agreement with QED predictions.
Limits on the anomalous magnetic and electric dipole moments of the tau lepton
are deduced.Comment: 20 pages, 9 figures, Accepted by Eur. Phys. J.
Evidence for an Excess of Soft Photons in Hadronic Decays of Z^0
Soft photons inside hadronic jets converted in front of the DELPHI main
tracker (TPC) in events of qqbar disintegrations of the Z^0 were studied in the
kinematic range 0.2 < E_gamma < 1 GeV and transverse momentum with respect to
the closest jet direction p_T < 80 MeV/c. A clear excess of photons in the
experimental data as compared to the Monte Carlo predictions is observed. This
excess (uncorrected for the photon detection efficiency) is (1.17 +/- 0.06 +/-
0.27) x 10^{-3} gamma/jet in the specified kinematic region, while the expected
level of the inner hadronic bremsstrahlung (which is not included in the Monte
Carlo) is (0.340 +/- 0.001 +/- 0.038) x 10^{-3} gamma/jet. The ratio of the
excess to the predicted bremsstrahlung rate is then (3.4 +/- 0.2 +/- 0.8),
which is similar in strength to the anomalous soft photon signal observed in
fixed target experiments with hadronic beams.Comment: 37 pages, 9 figures, Accepted by Eur. Phys. J.
A Measurement of the Tau Hadronic Branching Ratios
The exclusive and semi-exclusive branching ratios of the tau lepton hadronic
decay modes (h- v_t, h- pi0 v_t, h- pi0 pi0 v_t, h- \geq 2pi0 v_t, h- \geq 3pi0
v_t, 2h- h+ v_t, 2h- h+ pi0 v_t, 2h- h+ \geq 2pi0 v_t, 3h- 2h+ v_t and 3h- 2h+
\geq 1pi0 v_t) were measured with data from the DELPHI detector at LEP.Comment: 53 pages, 18 figures, Accepted by Eur. Phys. J.
Study of Leading Hadrons in Gluon and Quark Fragmentation
The study of quark jets in e+e- reactions at LEP has demonstrated that the
hadronisation process is reproduced well by the Lund string model. However, our
understanding of gluon fragmentation is less complete. In this study enriched
quark and gluon jet samples of different purities are selected in three-jet
events from hadronic decays of the Z collected by the DELPHI experiment in the
LEP runs during 1994 and 1995. The leading systems of the two kinds of jets are
defined by requiring a rapidity gap and their sum of charges is studied. An
excess of leading systems with total charge zero is found for gluon jets in all
cases, when compared to Monte Carlo Simulations with JETSET (with and without
Bose-Einstein correlations included) and ARIADNE. The corresponding leading
systems of quark jets do not exhibit such an excess. The influence of the gap
size and of the gluon purity on the effect is studied and a concentration of
the excess of neutral leading systems at low invariant masses (<~ 2 GeV/c^2) is
observed, indicating that gluon jets might have an additional hitherto
undetected fragmentation mode via a two-gluon system. This could be an
indication of a possible production of gluonic states as predicted by QCD.Comment: 19 pages, 6 figures, Accepted by Phys. Lett.
CP asymmetry in in a general two-Higgs-doublet model with fourth-generation quarks
We discuss the time-dependent CP asymmetry of decay in an
extension of the Standard Model with both two Higgs doublets and additional
fourth-generation quarks. We show that although the Standard Model with
two-Higgs-doublet and the Standard model with fourth generation quarks alone
are not likely to largely change the effective from the decay of
, the model with both additional Higgs doublet and
fourth-generation quarks can easily account for the possible large negative
value of without conflicting with other experimental
constraints. In this model, additional large CP violating effects may arise
from the flavor changing Yukawa interactions between neutral Higgs bosons and
the heavy fourth generation down type quark, which can modify the QCD penguin
contributions. With the constraints obtained from processes
such as and , this model can lead to the
effective to be as large as in the CP asymmetry of .Comment: 13 pages, 5 figures, references added, to appear in Eur.Phys.J.
Study of Inclusive J/psi Production in Two-Photon Collisions at LEP II with the DELPHI Detector
Inclusive J/psi production in photon-photon collisions has been observed at
LEP II beam energies. A clear signal from the reaction gamma gamma -> J/psi+X
is seen. The number of observed N(J/psi -> mu+mu-) events is 36 +/- 7 for an
integrated luminosity of 617 pb^{-1}, yielding a cross-section of
sigma(J/psi+X) = 45 +/- 9 (stat) +/- 17 (syst) pb. Based on a study of the
event shapes of different types of gamma gamma processes in the PYTHIA program,
we conclude that (74 +/- 22)% of the observed J/psi events are due to
`resolved' photons, the dominant contribution of which is most probably due to
the gluon content of the photon.Comment: 13 pages, 8 figures, Accepted by Phys. Lett.
- …