Al-Gazali skeletal dysplasia constitutes the lethal end of ADAMTSL2-related disorders

First published: 10 March 2023. OnlinePublLethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356) is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located.Dominyka Batkovskyte, Fiona McKenzie, Fulya Taylan, Pelin Ozlem Simsek-Kiper, Sarah M Nikkel, Hirofumi Ohashi, Roger E Stevenson, Thuong Ha, Denise P Cavalcanti, Hiroyuki Miyahara, Steven A Skinner, Miguel A Aguirre, Zühal Akçören, Gulen Eda Utine, Tillie Chiu, Kenji Shimizu, Anna Hammarsjö, Koray Boduroglu, Hannah W Moore, Raymond J Louie, Peer Arts, Allie N Merrihew, Milena Babic, Matilda R Jackson, Nikos Papadogiannakis, Anna Lindstrand, Ann Nordgren, Christopher P Barnett, Hamish S Scott, Andrei S Chagin, Gen Nishimura, and Giedre Grigelionien

The phenotype of Floating-Harbor syndrome: Clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results. Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from

An induced annual modulation signature in COSINE-100 data by DAMA/LIBRA’s analysis method

The DAMA/LIBRA collaboration has reported the observation of an annual modulation in the event rate that has been attributed to dark matter interactions over the last two decades. However, even though tremendous efforts to detect similar dark matter interactions were pursued, no definitive evidence has been observed to corroborate the DAMA/LIBRA signal. Many studies assuming various dark matter models have attempted to reconcile DAMA/LIBRA’s modulation signals and null results from other experiments, however no clear conclusion can be drawn. Apart from the dark matter hypothesis, several studies have examined the possibility that the modulation is induced by variations in detector’s environment or their specific analysis methods. In particular, a recent study presents a possible cause of the annual modulation from an analysis method adopted by the DAMA/LIBRA experiment in which the observed annual modulation could be reproduced by a slowly varying time-dependent background. Here, we study the COSINE-100 data using an analysis method similar to the one adopted by the DAMA/LIBRA experiment and observe a significant annual modulation, however the modulation phase is almost opposite to that of the DAMA/LIBRA data. Assuming the same background composition for COSINE-100 and DAMA/LIBRA, simulated experiments for the DAMA/LIBRA without dark matter signals also provide significant annual modulation with an amplitude similar to DAMA/LIBRA with opposite phase. Even though this observation does not directly explain the DAMA/LIBRA results directly, this interesting phenomenon motivates more profound studies of the time-dependent DAMA/LIBRA background data

Search for boosted dark matter in COSINE-100

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions

Search for bosonic super-weakly interacting massive particles at COSINE-100

We present results of a search for bosonic super-weakly interacting massive particles (BSW) as keV scale dark matter candidates that is based on an exposure of 97.7 kg·year from the COSINE experiment. In this search, we employ, for the first time, Compton-like as well as absorption processes for pseudoscalar and vector BSWs. No evidence for BSWs is found in the mass range from 10 keV/c2 to 1 MeV/c2, and we present the exclusion limits on the dimensionless coupling constants to electrons gae for pseudoscalar and κ for vector BSWs at 90% confidence level. Our results show that these limits are improved by including the Compton-like process in masses of BSW, above O(100 keV/c2)

Search for inelastic WIMP-iodine scattering with COSINE-100

We report the results of a search for inelastic scattering of weakly interacting massive particles (WIMPs) off I127 nuclei using NaI(Tl) crystals with a data exposure of 97.7 kg·years from the COSINE-100 experiment. The signature of inelastic WIMP-I127 scattering is a nuclear recoil accompanied by a 57.6 keV γ-ray from the prompt deexcitation, producing a more energetic signal compared to the typical WIMP nuclear recoil signal. We found no evidence for this inelastic scattering signature and set a 90% confidence level upper limit on the WIMP-proton spin-dependent, inelastic scattering cross section of 1.2×10-37 cm2 at the WIMP mass 500 GeV/c2

Search for solar bosonic dark matter annual modulation with COSINE-100

We present results from a search for solar bosonic dark matter using the annual modulation method with the COSINE-100 experiment. The results were interpreted considering three dark sector bosons models: solar dark photons, Dine-Fischler-Srednicki-Zhitnisky (DFSZ) and Kim-Shifman-Vainshtein-Zakharov (KSVZ) solar axions, and Kaluza-Klein solar axions. No modulation signal compatible with the expected from the models was found from a dataset of 2.82 yr, using 61.3 kg of NaI(Tl) crystals. Therefore, we set a 90% confidence level upper limits for each of the three models studied. For the solar dark photon model, the most stringent mixing parameter upper limit is 1.61×10-14 for dark photons with a mass of 215 eV. For the DFSZ and KSVZ solar axion, and the Kaluza-Klein axion models, the upper limits exclude axion-electron couplings, gae, above 1.61×10-11 for axion mass below 0.2 keV; and axion-photon couplings, gaγγ, above 1.83×10-11 GeV-1 for an axion number density of 4.07×1013 cm-3. This is the first experimental search for solar dark photons and DFSZ and KSVZ solar axions using the annual modulation method. The lower background, higher light yield and reduced threshold of NaI(Tl) crystals of the future COSINE-200 experiment are expected to enhance the sensitivity of the analysis shown in this paper. We show the sensitivities for the three models studied, considering the same search method with COSINE-200. © 2023 authors. Published by the American Physical Society. Published by the American Physical Society under the terms of the https://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI. Funded by SCOAP3.11Nsciescopu

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade

High Energy Physics Opportunities Using Reactor Antineutrinos

Nuclear reactors are uniquely powerful, abundant, and flavor-pure sources of antineutrinos that continue to play a vital role in the US neutrino physics program. The US reactor antineutrino physics community is a diverse interest group encompassing many detection technologies and many particle physics topics, including Standard Model and short-baseline oscillations, BSM physics searches, and reactor flux and spectrum modeling. The community's aims offer strong complimentary with numerous aspects of the wider US neutrino program and have direct relevance to most of the topical sub-groups composing the Snowmass 2021 Neutrino Frontier. Reactor neutrino experiments also have a direct societal impact and have become a strong workforce and technology development pipeline for DOE National Laboratories and universities. This white paper, prepared as a submission to the Snowmass 2021 community organizing exercise, will survey the state of the reactor antineutrino physics field and summarize the ways in which current and future reactor antineutrino experiments can play a critical role in advancing the field of particle physics in the next decade