The Exome Clinic and the role of medical genetics expertise in the interpretation of exome sequencing results.

Purpose: Evaluation of the clinician's role in the optimal interpretation of clinical exome sequencing (ES) results.

Methods: Retrospective chart review of the first 155 patients who underwent clinical ES in our Exome Clinic and direct interaction with the ordering geneticist to evaluate the process of interpretation of results.

Results: The most common primary indication was neurodevelopmental problems (~66%), followed by multiple congenital anomalies (~10%).

Multigenerational autosomal dominant inheritance of 5p chromosomal deletions.

Deletion of the short arm of chromosome 5 (5p-) is associated with phenotypic features including a cat-like cry in infancy, dysmorphic facial features, microcephaly, and intellectual disability, and when encompassing a minimal critical region, may be defined as Cri-du-Chat syndrome (CdCS). Most 5p deletions are de novo in origin, and familial cases are often associated with translocation and inversion. Herein, we report three multigenerational families carrying 5p terminal deletions of different size transmitted in an autosomal dominant manner causing variable clinical findings.

A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations.

The particular importance of Ca(2+) signaling to neurons demands its precise regulation within their cytoplasm. Isoform 3 of the plasma membrane Ca(2+) ATPase (the PMCA3 pump), which is highly expressed in brain and cerebellum, plays an important role in the regulation of neuronal Ca(2+). A genetic defect of the PMCA3 pump has been described in one family with X-linked congenital cerebellar ataxia.

Two novel RAD21 mutations in patients with mild Cornelia de Lange syndrome-like presentation and report of the first familial case.

Cornelia de Lange syndrome (CdLS) is a developmental disorder characterized by limb reduction defects, characteristic facial features and impaired cognitive development. Mutations in the NIPBL gene predominate; however, mutations in other cohesin complex genes have also been implicated, particularly in atypical and mild CdLS cases. Missense mutations and whole gene deletions in RAD21 have been identified in children with growth retardation, minor skeletal anomalies and facial features that overlap findings in individuals with CdLS.

Molecular and phenotypic characterization of atypical Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) is a multisystemic genomic disorder typically caused by a recurrent ˜1.5-1.8 Mb deletion on 7q11.

Hard two-body photodisintegration of 3He.

We have measured cross sections for the γ(3)He → pd reaction at photon energies of 0.4-1.4 GeV and a center-of-mass angle of 90°.

Effectiveness of topical anesthetics on reducing tactile sensitivity in the paws of newborn rats.

The aim of this study was to evaluate the effectiveness of three local, topical anesthetics on touch response thresholds of the paws of 1-day-old rats. Touch response thresholds were measured using Semmes Weinstein monofilaments after treatment of the paws with EMLA (2.5% lidocaine and 2.

Dynamics of West Nile virus persistence in House Sparrows (Passer domesticus).

West Nile Virus (WNV) is now endemic throughout North America, with annual recurrence dependent upon successful overwintering when cold temperatures drive mosquito vectors into inactivity and halt transmission. To investigate whether avian hosts may serve as an overwintering mechanism, groups of eight to ten House Sparrows were experimentally infected with a WN02 genotype of WNV and then held until necropsy at 3, 5, 7, 9, 12, 15, or 18 weeks post-infection (pi) when they were assessed for the presence of persistent infection. Blood was collected from all remaining birds every two weeks pi, and sera tested for WNV RNA and WNV neutralizing antibodies.

Measurement of exclusive π(0) electroproduction structure functions and their relationship to transverse generalized parton distributions.

Exclusive π(0) electroproduction at a beam energy of 5.75 GeV has been measured with the Jefferson Lab CLAS spectrometer. Differential cross sections were measured at more than 1800 kinematic values in Q(2), x(B), t, and ϕ(π), in the Q(2) range from 1.

Importance of recrudescent avian infection in West Nile virus overwintering: incomplete antibody neutralization of virus allows infrequent vector infection.

After the acute infection period, birds persistently infected with West Nile virus (family Flaviviridae, genus Flavivirus, WNV) occasionally shed virus into the bloodstream, but these virions normally are inactivated by neutralizing antibody. The current work tested the hypothesis that these host neutralizing antibodies protect mosquito vectors from WNV infection and reevaluated the minimum WNV infectious dose necessary to infect Culex tarsalis Coquillett. To determine whether host antibodies protect mosquitoes from infection, Cx.

Measurement of the neutron F2 structure function via spectator tagging with CLAS.

We report on the first measurement of the F(2) structure function of the neutron from the semi-inclusive scattering of electrons from deuterium, with low-momentum protons detected in the backward hemisphere. Restricting the momentum of the spectator protons to ≲100 MeV/c and their angles to ≳100° relative to the momentum transfer allows an interpretation of the process in terms of scattering from nearly on-shell neutrons. The F(2)(n) data collected cover the nucleon-resonance and deep-inelastic regions over a wide range of Bjorken x for 0.

Measurement of single- and double-spin asymmetries in deep inelastic pion electroproduction with a longitudinally polarized target.

We report the first measurement of the transverse momentum dependence of double-spin asymmetries in semi-inclusive production of pions in deep-inelastic scattering off the longitudinally polarized proton. Data have been obtained using a polarized electron beam of 5.7 GeV with the CLAS detector at the Jefferson Lab (JLab).

Tensor correlations measured in 3He(e,e' pp)n.

We have measured the 3He(e,e' pp)n reaction at an incident energy of 4.7 GeV over a wide kinematic range. We identified spectator correlated pp and pn nucleon pairs by using kinematic cuts and measured their relative and total momentum distributions.

Is low-grade serous ovarian cancer part of the tumor spectrum of hereditary breast and ovarian cancer?

Objective: To determine whether women with low-grade serous ovarian cancer (LGSOC) have personal and family histories of breast and ovarian cancer that are less suggestive of Hereditary Breast and Ovarian Cancer (HBOC), as compared to women with high-grade serous ovarian cancer (HGSOC).

Methods: A single institution, case-control retrospective review of medical records was conducted. Personal demographics, personal cancer history, and family history of breast and ovarian cancer of women with LGSOC were collected and compared to controls with HGSOC, which is known to be associated with HBOC.

Absorption of the ω and ϕ mesons in nuclei.

Because of their long lifetimes, the ω and ϕ mesons are the ideal candidates for the study of possible modifications of the in-medium meson-nucleon interaction through their absorption inside the nucleus. During the E01-112 experiment at the Thomas Jefferson National Accelerator Facility, the mesons were photoproduced from 2H, C, Ti, Fe, and Pb targets. This Letter reports the first measurement of the ratio of nuclear transparencies for the e+e- channel.

Precise measurement of the neutron magnetic form factor G(M)n in the few-GeV2 region.

The neutron elastic magnetic form factor was extracted from quasielastic electron scattering on deuterium over the range Q;{2}=1.0-4.8 GeV2 with the CLAS detector at Jefferson Lab.

Search for the photoexcitation of exotic mesons in the pi+pi+pi- system.

A search for exotic mesons in the pi;{+}pi;{+}pi;{-} system photoproduced by the charge exchange reaction gammap-->pi;{+}pi;{+}pi;{-}(n) was carried out by the CLAS Collaboration at Jefferson Lab. A tagged-photon beam with energies in the 4.8 to 5.

Measurement of direct f0(980) photoproduction on the proton.

We report on the results of the first measurement of exclusive f_{0}(980) meson photoproduction on protons for E_{gamma}=3.0-3.8 GeV and -t=0.

Measurement of deeply virtual compton scattering beam-spin asymmetries.

The beam-spin asymmetries in the hard exclusive electroproduction of photons on the proton (e p-->epgamma) were measured over a wide kinematic range and with high statistical accuracy. These asymmetries result from the interference of the Bethe-Heitler process and of deeply virtual Compton scattering. Over the whole kinematic range (x(B) from 0.

Bayesian analysis of pentaquark signals from CLAS data.

We examine the results of two measurements by the CLAS collaboration, one of which claimed evidence for a Theta(+) pentaquark, while the other found no such evidence. The unique feature of these two experiments was that they were performed with the same experimental setup. Using a Bayesian analysis, we find that the results of the two experiments are in fact compatible with each other, but that the first measurement did not contain sufficient information to determine unambiguously the existence of a Theta(+).

Search for medium modifications of the rho meson.

The photoproduction of vector mesons on various nuclei has been studied using the CLAS detector at Jefferson Laboratory. The vector mesons, rho, omega, and varphi, are observed via their decay to e;{+}e;{-}, in order to reduce the effects of final-state interactions in the nucleus. Of particular interest are possible in-medium effects on the properties of the rho meson.

Experimental study of exclusive 2H(e,e'p)n reaction mechanisms at high Q2.

The reaction 2H(e,e'p)n has been studied with full kinematic coverage for photon virtuality 1.75 View Article and Find Full Text PDF

Measurement of deeply virtual compton scattering with a polarized-proton target.

The longitudinal target-spin asymmetry AUL for the exclusive electroproduction of high-energy photons was measured for the first time in ep-->e;'pgamma. The data have been accumulated at JLab with the CLAS spectrometer using 5.7 GeV electrons and a longitudinally polarized NH3 target.