2,207 research outputs found
Evaluation of autosomal dominant retinal dystrophy genes in an unaffected cohort suggests rare or private missense variants may often be benign.
BackgroundMany genes have been reported as harboring autosomal dominant mutations causing retinal dystrophy. As newly available gene panel sequencing and whole exome sequencing will open these genes up to greater scrutiny, we assess the rate of rare coding variation in these genes among unaffected individuals to provide context for variants that will be discovered when clinical subjects are sequenced.MethodsPublicly available data from the Exome Variant Project were analyzed, focusing on 36 genes known to harbor mutations causing autosomal dominant macular dystrophy.ResultsRates of rare (minor allele frequency â€0.1%) and private missense variants within autosomal dominant retinal dystrophy genes were found to occur at a high frequency in unaffected individuals, while nonsense variants were not.ConclusionsWe conclude that rare missense variations in most of these genes identified in individuals with retinal dystrophy cannot be confidently classified as disease-causing in the absence of additional information such as linkage or functional validation
De Novo Occurrence of a Variant in ARL3 and Apparent Autosomal Dominant Transmission of Retinitis Pigmentosa.
BackgroundRetinitis pigmentosa is a phenotype with diverse genetic causes. Due to this genetic heterogeneity, genome-wide identification and analysis of protein-altering DNA variants by exome sequencing is a powerful tool for novel variant and disease gene discovery. In this study, exome sequencing analysis was used to search for potentially causal DNA variants in a two-generation pedigree with apparent dominant retinitis pigmentosa.MethodsVariant identification and analysis of three affected members (mother and two affected offspring) was performed via exome sequencing. Parental samples of the index case were used to establish inheritance. Follow-up testing of 94 additional retinitis pigmentosa pedigrees was performed via retrospective analysis or Sanger sequencing.Results and conclusionsA total of 136 high quality coding variants in 123 genes were identified which are consistent with autosomal dominant disease. Of these, one of the strongest genetic and functional candidates is a c.269A>G (p.Tyr90Cys) variant in ARL3. Follow-up testing established that this variant occurred de novo in the index case. No additional putative causal variants in ARL3 were identified in the follow-up cohort, suggesting that if ARL3 variants can cause adRP it is an extremely rare phenomenon
Congenital myasthenic syndrome caused by a frameshift insertion mutation in
Objective: Description of a new variant of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) gene causing congenital myasthenic syndrome (CMS) in 3 children from 2 unrelated families.
Methods: Muscle biopsies, EMG, and whole-exome sequencing were performed.
Results: All 3 patients presented with congenital hypotonia, muscle weakness, respiratory insufficiency, head lag, areflexia, and gastrointestinal dysfunction. Genetic analysis identified a homozygous frameshift insertion in the GFPT1 gene (NM_001244710.1: c.686dupC; p.Arg230Ter) that was shared by all 3 patients. In one of the patients, inheritance of the variant was through uniparental disomy (UPD) with maternal origin. Repetitive nerve stimulation and single-fiber EMG was consistent with the clinical diagnosis of CMS with a postjunctional defect. Ultrastructural evaluation of the muscle biopsy from one of the patients showed extremely attenuated postsynaptic folds at neuromuscular junctions and extensive autophagic vacuolar pathology.
Conclusions: These results expand on the spectrum of known loss-of-function GFPT1 mutations in CMS12 and in one family demonstrate a novel mode of inheritance due to UPD
A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)
We present a measurement of time-dependent CP-violating asymmetries in
neutral B meson decays collected with the BABAR detector at the PEP-II
asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data
sample consists of 29.7 recorded at the
resonance and 3.9 off-resonance. One of the neutral B mesons,
which are produced in pairs at the , is fully reconstructed in
the CP decay modes , , , () and , or in flavor-eigenstate
modes involving and (). The flavor of the other neutral B meson is tagged at the time of
its decay, mainly with the charge of identified leptons and kaons. The proper
time elapsed between the decays is determined by measuring the distance between
the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample
finds . The value of the asymmetry amplitude is determined from
a simultaneous maximum-likelihood fit to the time-difference distribution of
the flavor-eigenstate sample and about 642 tagged decays in the
CP-eigenstate modes. We find , demonstrating that CP violation exists in the neutral B meson
system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review
Measurement of the Branching Fraction for B- --> D0 K*-
We present a measurement of the branching fraction for the decay B- --> D0
K*- using a sample of approximately 86 million BBbar pairs collected by the
BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is
detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the
K*- through its decay to K0S pi-. We measure the branching fraction to be
B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid
Communications
Evidence for the Rare Decay B -> K*ll and Measurement of the B -> Kll Branching Fraction
We present evidence for the flavor-changing neutral current decay and a measurement of the branching fraction for the related
process , where is either an or
pair. These decays are highly suppressed in the Standard Model,
and they are sensitive to contributions from new particles in the intermediate
state. The data sample comprises
decays collected with the Babar detector at the PEP-II storage ring.
Averaging over isospin and lepton flavor, we obtain the branching
fractions and , where the
uncertainties are statistical and systematic, respectively. The significance of
the signal is over , while for it is .Comment: 7 pages, 2 postscript figues, submitted to Phys. Rev. Let
Study of e+e- --> pi+ pi- pi0 process using initial state radiation with BABAR
The process e+e- --> pi+ pi- pi0 gamma has been studied at a center-of-mass
energy near the Y(4S) resonance using a 89.3 fb-1 data sample collected with
the BaBar detector at the PEP-II collider. From the measured 3pi mass spectrum
we have obtained the products of branching fractions for the omega and phi
mesons, B(omega --> e+e-)B(omega --> 3pi)=(6.70 +/- 0.06 +/- 0.27)10-5 and
B(phi --> e+e-)B(phi --> 3pi)=(4.30 +/- 0.08 +/- 0.21)10-5, and evaluated the
e+e- --> pi+ pi- pi0 cross section for the e+e- center-of-mass energy range
1.05 to 3.00 GeV. About 900 e+e- --> J/psi gamma --> pi+ pi- pi0 gamma events
have been selected and the branching fraction B(J/psi --> pi+ pi- pi0)=(2.18
+/- 0.19)% has been measured.Comment: 21 pages, 37 postscript figues, submitted to Phys. Rev.
Measurement of Branching Fraction and Dalitz Distribution for B0->D(*)+/- K0 pi-/+ Decays
We present measurements of the branching fractions for the three-body decays
B0 -> D(*)-/+ K0 pi^+/-B0 -> D(*)-/+ K*+/- using
a sample of approximately 88 million BBbar pairs collected by the BABAR
detector at the PEP-II asymmetric energy storage ring.
We measure:
B(B0->D-/+ K0 pi+/-)=(4.9 +/- 0.7(stat) +/- 0.5 (syst)) 10^{-4}
B(B0->D*-/+ K0 pi+/-)=(3.0 +/- 0.7(stat) +/- 0.3 (syst)) 10^{-4}
B(B0->D-/+ K*+/-)=(4.6 +/- 0.6(stat) +/- 0.5 (syst)) 10^{-4}
B(B0->D*-/+ K*+/-)=(3.2 +/- 0.6(stat) +/- 0.3 (syst)) 10^{-4}
From these measurements we determine the fractions of resonant events to be :
f(B0-> D-/+ K*+/-) = 0.63 +/- 0.08(stat) +/- 0.04(syst) f(B0-> D*-/+ K*+/-) =
0.72 +/- 0.14(stat) +/- 0.05(syst)Comment: 7 pages, 3 figures submitted to Phys. Rev. Let
Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions
The weak nucleon axial-vector form factor for quasi-elastic interactions is
determined using neutrino interaction data from the K2K Scintillating Fiber
detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of
which half are charged-current quasi-elastic interactions nu-mu n to mu- p
occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for
oxygen and assume the form factor is approximately a dipole with one parameter,
the axial vector mass M_A, and fit to the shape of the distribution of the
square of the momentum transfer from the nucleon to the nucleus. Our best fit
result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated
vector form factors from recent electron scattering experiments and a
discussion of the effects of the nucleon momentum on the shape of the fitted
distributions.Comment: 14 pages, 10 figures, 6 table
Measurement of the B+ --> p pbar K+ Branching Fraction and Study of the Decay Dynamics
With a sample of 232x10^6 Upsilon(4S) --> BBbar events collected with the
BaBar detector, we study the decay B+ --> p pbar K+ excluding charmonium decays
to ppbar. We measure a branching fraction Br(B+ --> p pbar
K+)=(6.7+/-0.5+/-0.4)x10^{-6}. An enhancement at low ppbar mass is observed and
the Dalitz plot asymmetry suggests dominance of the penguin amplitude in this B
decay. We search for a pentaquark candidate Theta*++ decaying into pK+ in the
mass range 1.43 to 2.00 GeV/c2 and set limits on Br(B+ -->
Theta*++pbar)xBr(Theta*++ --> pK+) at the 10^{-7} level.Comment: 8 pages, 7 postscript figures, submitted to Phys. Rev. D (Rapid
Communications
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