The role of next-generation sequencing in the diagnosis of lysosomal storage disorders

Next-generation sequencing (NGS) panels are used widely in clinical diagnostics to identify genetic causes of various monogenic disease groups including neurometabolic disorders and, more recently, lysosomal storage disorders. Many new challenges have been introduced through these new technologies, both at the laboratory level and at the bioinformatics level, with consequences including new requirements for interpretation of results, and for genetic counseling. We review some recent examples of the application of NGS technologies, with purely diagnostic and with both diagnostic and research aims, for establishing a rapid genetic diagnosis in lysosomal storage disorders. Given that NGS can be applied in a way that takes into account the many issues raised by international consensus guidelines, it can have a significant role even early in the course of the diagnostic process, in combination with biochemical and clinical data. Besides decreasing the delay in diagnosis for many patients, a precise molecular diagnosis is extremely important as new therapies are becoming available within the LSD disease spectrum for patients who share specific types of mutations. A genetic diagnosis is also the prerequisite for genetic counseling, family planning and the individual choice of reproductive options in affected families

From band insulator to Mott insulator in one dimension

We derive the phase diagram for the one-dimensional model of a ferroelectric perovskite recently introduced by Egami, Ishihara and Tachiki [Science, {\bf 261}, 1307 (1993)]. We show that the interplay between covalency, ionicity and strong correlations results in a spontaneously dimerized phase which separates the weak-coupling band insulator from the strong-coupling Mott insulator. The transition from the band insulator to the dimerized phase is identified as an Ising critical point. The charge gap vanishes at this single point with the optical conductivity diverging as $\sigma(\omega)\sim \omega^{-3/4}$. The spin excitations are gapless above the second transition to the Mott insulator phase.Comment: 4 pages LaTex (RevTex) and 1 postscript figure included by eps

Inter-Edge interaction in the Quantum Hall Effect

We consider effects of the interaction between electrons drifting along the opposite sides of a narrow sample under the conditions of the quantum Hall effect. A spatial variation of this interaction leads to backward scattering of collective excitations propagating along the edges. Experiments on propagation of the edge modes in samples with constrictions may give information about the strength of the inter-edge electron interaction in the quantum Hall regime.Comment: 12 Pages, Latex, Accepted for publication in PRL

Interacting one dimensional electron gas with open boundaries

We discuss the properties of interacting electrons on a finite chain with open boundary conditions. We extend the Haldane Luttinger liquid description to these systems and study how the presence of the boundaries modifies various correlation functions. In view of possible experimental applications to quantum wires, we analyse how tunneling measurements can reveal the underlying Luttinger liquid properties. The two terminal conductance is calculated. We also point out possible applications to quasi one dimensional materials and study the effects of magnetic impurities.Comment: 38 pages, ReVTeX, 7 figures (available upon request

Resonance in One--Dimensional Fermi--Edge Singularity

The problem of the Fermi--edge singularity in a one--dimensional Tomonaga--Luttinger liquid is reconsidered. The backward scattering of the conduction band electrons on the impurity--like hole in the valence band is analyzed by mapping the problem onto a Coulomb gas theory. For the case when the electron--electron interaction is repulsive the obtained exponent of the one--dimensional Fermi--edge singularity appears to be different from the exponent found in the previous studies. It is shown that the infrared physics of the Fermi--edge singularity in the presence of backward scattering and electron--electron repulsion resembles the physics of the Kondo problem.Comment: 38 pages and 1 figure, to be published in PR

The Role of Next-Generation Sequencing in the Diagnosis of Lysosomal Storage Disorders

Next-generation sequencing (NGS) panels are used widely in clinical diagnostics to identify genetic causes of various monogenic disease groups including neurometabolic disorders and, more recently, lysosomal storage disorders (LSDs). Many new challenges have been introduced through these new technologies, both at the laboratory level and at the bioinformatics level, with consequences including new requirements for interpretation of results, and for genetic counseling. We review some recent examples of the application of NGS technologies, with purely diagnostic and with both diagnostic and research aims, for establishing a rapid genetic diagnosis in LSDs. Given that NGS can be applied in a way that takes into account the many issues raised by international consensus guidelines, it can have a significant role even early in the course of the diagnostic process, in combination with biochemical and clinical data. Besides decreasing the delay in diagnosis for many patients, a precise molecular diagnosis is extremely important as new therapies are becoming available within the LSD spectrum for patients who share specific types of mutations. A genetic diagnosis is also the prerequisite for genetic counseling, family planning, and the individual choice of reproductive options in affected families

Immunogenicity of a 2009 pandemic influenza virus A H1N1 vaccine, administered simultaneously with the seasonal influenza vaccine, in children receiving chemotherapy.

BACKGROUND: No examination of simultaneous vaccination against pandemic H1N1 and the seasonal influenza virus strains, in children with cancer receiving chemotherapy, are yet published. We investigated the immunogenicity of a whole-virion, inactivated, adjuvanted pandemic H1N1, and seasonal influenza vaccines administered simultaneously to children with cancer undergoing chemotherapy. PROCEDURE: We prospectively enrolled 27 pediatric patients receiving therapy for various types of cancer. All received influenza vaccination once in a seasonal risk period. We checked hemaglutination-inhibition (HAI) antibody titers in the sera of patients before, and 21-28 days after vaccination. Seroprotective titer was defined as an antibody titer >/=40, and seroresponse as >/=4-fold increase in antibody titers after vaccination. RESULTS: The pre- and post-vaccination seroprotective rates were H1N1: 33-48%, H3N2: 56-78%, B: 0-15% for seasonal influenza, and for pandemic H1N1: 15-37%. The seroresponse rates for seasonal influenza H1N1, H3N2, and B were 22%, 37%, and 22%, respectively, and 30% for the pandemic H1N1 vaccine. CONCLUSIONS: Whole-virion, inactivated, adjuvanted vaccine for the pandemic H1N1 Influenza A virus and the seasonal influenza vaccines were found safe and partially immunogenic in children with cancer receiving chemotherapy. The only determinants of responsiveness were lymphocyte count and serum immunoglobulin-G. Only influenza B vaccine elicited significant differences in differences in pre- and post-vaccination seroprotective rates. The response to vaccination for pandemic H1N1 is as effective as other vaccines, however administration of a single vaccine during chemotherapy is more comfortable for pediatric cancer patients. Pediatr Blood Cancer (c) 2014 Wiley Periodicals, Inc