Phenotypic variability of patients homozygous for the GJB2 mutation 35delG cannot be explained by the influence of one major modifier gene

Hereditary hearing loss (HL) is a very heterogeneous trait, with 46 gene identifications for non-syndromic HL. Mutations in GJB2 cause up to half of all cases of severe-to-profound congenital autosomal recessive non-syndromic HL, with 35delG being the most frequent mutation in Caucasians. Although a genotype-phenotype correlation has been established for most GJB2 genotypes, the HL of 35delG homozygous patients is mild to profound. We hypothesise that this phenotypic variability is at least partly caused by the influence of modifier genes. By performing a whole-genome association (WGA) study on 35delG homozygotes, we sought to identify modifier genes. The association study was performed by comparing the genotypes of mild/moderate cases and profound cases. The first analysis included a pooling-based WGA study of a first set of 255 samples by using both the Illumina 550K and Affymetrix 500K chips. This analysis resulted in a ranking of all analysed single-nucleotide polymorphisms (SNPs) according to their P-values. The top 250 most significantly associated SNPs were genotyped individually in the same sample set. All 192 SNPs that still had significant P-values were genotyped in a second independent set of 297 samples for replication. The significant P-values were replicated in nine SNPs, with combined P-values between 3 x 10(-3) and 1 x 10(-4). This study suggests that the phenotypic variability in 35delG homozygous patients cannot be explained by the effect of one major modifier gene. Significantly associated SNPs may reflect a small modifying effect on the phenotype. Increasing the power of the study will be of greatest importance to confirm these results

GJB2 mutations and degree of hearing loss: a multicenter study.

Contains fulltext : 47828.pdf (publisher's version ) (Closed access)Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P<.0001). The HI of 48 different genotypes was less severe than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mild-to-moderate HI (median 25-40 dB). Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes

Proton reconstruction with the CMS-TOTEM Precision Proton Spectrometer

International audienceThe Precision Proton Spectrometer (PPS) of the CMS and TOTEM experiments collected 107.7 fb$^{-1}$ in proton-proton (pp) collisions at the LHC at 13 TeV (Run 2). This paper describes the key features of the PPS alignment and optics calibrations, the proton reconstruction procedure, as well as the detector efficiency and the performance of the PPS simulation. The reconstruction and simulation are validated using a sample of (semi)exclusive dilepton events. The performance of PPS has proven the feasibility of continuously operating a near-beam proton spectrometer at a high luminosity hadron collider

Measurement of single-diffractive dijet production in proton-proton collisions at s=\sqrt{s} =s​= 8 TeV with the CMS and TOTEM experiments

Measurements are presented of the single-diffractive dijet cross section and the diffractive cross section as a function of the proton fractional momentum loss $\xi$ and the four-momentum transfer squared t. Both processes ${\text{ p }{}{}} {\text{ p }{}{}} \rightarrow {\text{ p }{}{}} {\text{ X }}$ and ${\text{ p }{}{}} {\text{ p }{}{}} \rightarrow {\text{ X }} {\text{ p }{}{}}$, i.e. with the proton scattering to either side of the interaction point, are measured, where ${\text{ X }}$ includes at least two jets; the results of the two processes are averaged. The analyses are based on data collected simultaneously with the CMS and TOTEM detectors at the LHC in proton–proton collisions at $\sqrt{s} = 8\,\text {Te}\text {V}$ during a dedicated run with $\beta ^{*} = 90\,\text {m}$ at low instantaneous luminosity and correspond to an integrated luminosity of $37.5{\,\text {nb}^{-1}}$. The single-diffractive dijet cross section $\sigma ^{{\text{ p }{}{}} {\text{ X }}}_{\mathrm {jj}}$, in the kinematic region $\xi 40\,\text {Ge}\text {V}$, and pseudorapidity $|\eta | < 4.4$, is 21.7 \pm 0.9\,\text {(stat)} \,^{+3.0}_{-3.3}\,\text {(syst)} \pm 0.9\,\text {(lumi)} \,\text {nb} . The ratio of the single-diffractive to inclusive dijet yields, normalised per unit of $\xi$, is presented as a function of x, the longitudinal momentum fraction of the proton carried by the struck parton. The ratio in the kinematic region defined above, for x values in the range $-2.9 \le \log _{10} x \le -1.6$, is $R = (\sigma ^{{\text{ p }{}{}} {\text{ X }}}_{\mathrm {jj}}/\Delta \xi )/\sigma _{\mathrm {jj}} = 0.025 \pm 0.001\,\text {(stat)} \pm 0.003\,\text {(syst)}$, where $\sigma ^{{\text{ p }{}{}} {\text{ X }}}_{\mathrm {jj}}$ and $\sigma _{\mathrm {jj}}$ are the single-diffractive and inclusive dijet cross sections, respectively. The results are compared with predictions from models of diffractive and nondiffractive interactions. Monte Carlo predictions based on the HERA diffractive parton distribution functions agree well with the data when corrected for the effect of soft rescattering between the spectator partons

A search for new physics in central exclusive production using the missing mass technique with the CMS detector and the CMS-TOTEM precision proton spectrometer

International audienceA generic search is presented for the associated production of a Z boson or a photon with an additional unspecified massive particle X, pp $\to$ pp + Z/$\gamma$ + X, in proton-tagged events from proton-proton collisions at $\sqrt{s}$ = 13 TeV, recorded in 2017 with the CMS detector and the CMS-TOTEM precision proton spectrometer. The missing mass spectrum is analysed in the 600-1600 GeV range and a fit is performed to search for possible deviations from the background expectation. No significant excess in data with respect to the background predictions has been observed. Model-independent upper limits on the visible production cross section of pp $\to$ pp + Z/$\gamma$ + X are set

First search for exclusive diphoton production at high mass with tagged protons in proton-proton collisions at s=\sqrt{s} = 13 TeV

A search for exclusive two-photon production via photon exchange in proton-proton collisions, pp $\to$ p$\gamma\gamma$p with intact protons, is presented. The data correspond to an integrated luminosity of 9.4 fb$^{-1}$ collected in 2016 using the CMS and TOTEM detectors at a center-of-mass energy of 13 TeV at the LHC. Events are selected with a diphoton invariant mass above 350 GeV and with both protons intact in the final state, to reduce backgrounds from strong interactions. The events of interest are those where the invariant mass and rapidity calculated from the momentum losses of the forward-moving protons matches the mass and rapidity of the central, two-photon system. No events are found that satisfy this condition. Interpreting this result in an effective dimension-8 extension of the standard model, the first limits are set on the two anomalous four-photon coupling parameters. If the other parameter is constrained to its standard model value, the limits at 95% CL are $\lvert\zeta_1\rvert$ $\lt$ 2.9 $\times$ 10$^{-13}$ GeV$^{-4}$ and $\lvert\zeta_2\rvert$ $\lt$ 6.0 $\times$ 10$^{-13}$ GeV$^{-4}$

Hard color-singlet exchange in dijet events in proton-proton collisions at s=\sqrt{s} = 13 TeV

International audienceEvents where the two leading jets are separated by a pseudorapidity interval devoid of particle activity, known as jet-gap-jet events, are studied in proton-proton collisions at $\sqrt{s} =$ 13 TeV. The signature is expected from hard color-singlet exchange. Each of the highest transverse momentum ($p_\mathrm{T}$) jets must have $p_\mathrm{T}^\text{jet}$$\gt$ 40 GeV and pseudorapidity 1.4 $\lt$$|\eta^\text{jet}|$$\lt$ 4.7, with $\eta^\text{jet1} \eta^\text{jet2}$$\lt$ 0, where $\text{jet1}$ and $\text{jet2}$ are the leading and subleading jets in $p_\mathrm{T}$, respectively. The analysis is based on data collected by the CMS and TOTEM experiments during a low luminosity, high-$\beta^*$ run at the CERN LHC in 2015, with an integrated luminosity of 0.66 pb$^{-1}$. Events with a low number of charged particles with $p_\mathrm{T}$$\gt$ 0.2 GeV in the interval $|\eta|$$\lt$ 1 between the jets are observed in excess of calculations that assume only color-exchange. The fraction of events produced via color-singlet exchange, $f_\text{CSE}$, is measured as a function of $p_\mathrm{T}^\text{jet2}$, the pseudorapidity difference between the two leading jets, and the azimuthal angular separation between the two leading jets. The fraction $f_\text{CSE}$ has values of 0.4-1.0%. The results are compared with previous measurements and with predictions from perturbative quantum chromodynamics. In addition, the first study of jet-gap-jet events detected in association with an intact proton using a subsample of events with an integrated luminosity of 0.40 pb$^{-1}$ is presented. The intact protons are detected with the Roman pot detectors of the TOTEM experiment. The $f_\text{CSE}$ in this sample is 2.91 $\pm$ 0.70 (stat) $^{+1.08}_{-1.01}$ (syst) times larger than that for inclusive dijet production in dijets with similar kinematics

First search for exclusive diphoton production at high mass with tagged protons in proton-proton collisions at s=\sqrt{s} = 13 TeV

International audienceA search for exclusive two-photon production via photon exchange in proton-proton collisions, pp $\to$ p$\gamma\gamma$p with intact protons, is presented. The data correspond to an integrated luminosity of 9.4 fb$^{-1}$ collected in 2016 using the CMS and TOTEM detectors at a center-of-mass energy of 13 TeV at the LHC. Events are selected with a diphoton invariant mass above 350 GeV and with both protons intact in the final state, to reduce backgrounds from strong interactions. The events of interest are those where the invariant mass and rapidity calculated from the momentum losses of the forward-moving protons matches the mass and rapidity of the central, two-photon system. No events are found that satisfy this condition. Interpreting this result in an effective dimension-8 extension of the standard model, the first limits are set on the two anomalous four-photon coupling parameters. If the other parameter is constrained to its standard model value, the limits at 95% CL are $\lvert\zeta_1\rvert$ $\lt$ 2.9 $\times$ 10$^{-13}$ GeV$^{-4}$ and $\lvert\zeta_2\rvert$ $\lt$ 6.0 $\times$ 10$^{-13}$ GeV$^{-4}$