340 research outputs found
ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease
Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for similar to 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot-Marie-Tooth disease type 2H on chromosome 8q13-21.1 was excluded by linkage analysis. Pedigrees originated in Italy, Brazil, Canada, England, Iran, and Japan. Interestingly, we identified 15 ALS5/SPG11/KIAA1840 mutations in 12 families (two sequence variants were never reported before, p.Gln198* and p.Pro2212fs*5). No large deletions/duplications were detected in these patients. The novel mutations seemed to be pathogenic since they co-segregated with the disease in all pedigrees and were absent in 300 unrelated controls. Furthermore, in silico analysis predicted their pathogenic effect. Our results indicate that ALS5/SPG11/KIAA1840 is the causative gene of a wide spectrum of clinical features, including autosomal recessive axonal Charcot-Marie-Tooth disease
Frameshift mutations at the C-terminus of HIST1H1E result in a specific DNA hypomethylation signature
BACKGROUND: We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern. RESULTS: Methylome analysis from peripheral blood samples of six affected subjects led us to identify a specific hypomethylated profile. This "episignature" was enriched for genes involved in neuronal system development and function. A computational classifier yielded full sensitivity and specificity in detecting subjects with Rahman syndrome. Applying this model to a cohort of undiagnosed probands allowed us to reach diagnosis in one subject. CONCLUSIONS: We demonstrate an epigenetic signature in subjects with Rahman syndrome that can be used to reach molecular diagnosis
Search for Branons at LEP
We search, in the context of extra-dimension scenarios, for the possible
existence of brane fluctuations, called branons. Events with a single photon or
a single Z-boson and missing energy and momentum collected with the L3 detector
in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are
analysed. No excess over the Standard Model expectations is found and a lower
limit at 95% confidence level of 103 GeV is derived for the mass of branons,
for a scenario with small brane tensions. Alternatively, under the assumption
of a light branon, brane tensions below 180 GeV are excluded
Search for Branons at LEP
We search, in the context of extra-dimension scenarios, for the possible
existence of brane fluctuations, called branons. Events with a single photon or
a single Z-boson and missing energy and momentum collected with the L3 detector
in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are
analysed. No excess over the Standard Model expectations is found and a lower
limit at 95% confidence level of 103 GeV is derived for the mass of branons,
for a scenario with small brane tensions. Alternatively, under the assumption
of a light branon, brane tensions below 180 GeV are excluded
Study of Spin and Decay-Plane Correlations of W Bosons in the e+e- -> W+W- Process at LEP
Data collected at LEP at centre-of-mass energies \sqrt(s) = 189 - 209 GeV are
used to study correlations of the spin of W bosons using e+e- -> W+W- -> lnqq~
events. Spin correlations are favoured by data, and found to agree with the
Standard Model predictions. In addition, correlations between the W-boson decay
planes are studied in e+e- -> W+W- -> lnqq~ and e+e- -> W+W- -> qq~qq~ events.
Decay-plane correlations, consistent with zero and with the Standard Model
predictions, are measured
Ultrarelativistic sources in nonlinear electrodynamics
The fields of rapidly moving sources are studied within nonlinear
electrodynamics by boosting the fields of sources at rest. As a consequence of
the ultrarelativistic limit the delta-like electromagnetic shock waves are
found. The character of the field within the shock depends on the theory of
nonlinear electrodynamics considered. In particular, we obtain the field of an
ultrarelativistic charge in the Born-Infeld theory.Comment: 10 pages, 3 figure
Measurement of Exclusive rho^0 rho^0 Production in Two-Photon Collisions at High Q^2 at LEP
Exclusive rho rho production in two-photon collisions involving a single
highly virtual photon is studied with data collected at LEP at centre-of-mass
energies 89GeV < \sqrt{s} < 209GeV with a total integrated luminosity of
854.7pb^-1 The cross section of the process gamma gamma^* -> rho rho is
determined as a function of the photon virtuality, Q^2 and the two-photon
centre-of-mass energy, Wgg, in the kinematic region: 1.2GeV^2 < Q^2 < 30GeV^2
and 1.1GeV < Wgg < 3GeV
Measurement of the Cross Section for Open-Beauty Production in Photon-Photon Collisions at LEP
The cross section for open-beauty production in photon-photon collisions is
measured using the whole high-energy and high-luminosity data sample collected
by the L3 detector at LEP. This corresponds to 627/pb of integrated luminosity
for electron-positron centre-of-mass energies from 189GeV to 209GeV. Events
containing b quarks are identified through their semi-leptonic decay into
electrons or muons. The e+e- -> e+e-b b~X cross section is measured within our
fiducial volume and then extrapolated to the full phase space. These results
are found to be in significant excess with respect to Monte Carlo predictions
and next-to-leading order QCD calculations
Formation of the in Two-Photon Collisions at LEP
The two-photon width of the meson has been
measured with the L3 detector at LEP. The is studied in the decay
modes , KK, KK,
KK, , , and
using an integrated luminosity of 140 pb at GeV and
of 52 pb at GeV. The result is
(BR) keV. The dependence of the cross section is studied for
GeV. It is found to be better described by a Vector Meson
Dominance model form factor with a J-pole than with a -pole. In addition,
a signal of events is observed at the mass. Upper limits
for the two-photon widths of the , , and are also
given
Search for Heavy Isosinglet Neutrino in e+e- Annihilation at LEP
We report on a search for the first generation heavy neutrino that is an
isosinglet under the standard SU(2)_L gauge group. The data collected with the
L3 detector at center-of-mass energies between 130 GeV and 208 GeV are used.The
decay channel N_e --> eW is investigated and no evidence is found for a heavy
neutrino, N_e, in a mass range between 80 GeV and 205 GeV. Upper limits on the
mixing parameter between the heavy and light neutrino are derived
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