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《European journal of medical genetics》2022,65(6):104495
Spondyloepimetaphyseal dysplasias (SEMDs) belong to a clinically and genetically heterogeneous group of inherited skeletal disorders defined by a defect in the growth and shape of vertebrae, epiphyses and metaphyses. Rhizomelic SEMD is characterized by a disproportionate small stature caused by severe shortening and deformation of the limbs’ proximal bones, with the cranio-facial sphere unaffected. We report a second individual, an 8-year-old girl, with autosomal recessive rhizomelic SEMD associated with a homozygous exonic missense variant, c.226G > A p.(Glu76Lys), in GNPNAT1 identified by trio genome sequencing. Our data corroborate the recent findings of Ain et al. and further delineate the clinical and radiographic features of this form of SEMD associated with rhizomelic dysplasia while outlining a potential hotspot in this newly described genetic disorder. 相似文献
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The study aimed to evaluate the impact of the updated 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) testing in invasive breast cancer compared with previous 2013 guidelines. Between Jan 2014 and May 2020, 3364 consecutive invasive breast carcinomas with concurrent HER2 immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) results were retrospectively reviewed for HER2 status. Both 2013 and 2018 testing criteria were applied to establish the HER2 status. The testing algorithms involved testing of invasive breast carcinomas by IHC, with equivocal results being reflexed to FISH assays. Concordance rate improved from 92.7% to 94.1% in the non-equivocal IHC cases with the 2018 guidelines. Comparing 2013 versus 2018 criteria, HER2 non-amplified cases increased significantly from 73.7% (n = 2478) to 76.8% (n = 2585), HER2 amplified cases remained similar from 23.4% (n = 789) to 23.2% (n = 779) while equivocal cases decreased from 2.9% (n = 97) to 0% with the new guidelines. Thus, 107 cases (3.2%) were reclassified from HER2 equivocal (n = 97) and amplified (n = 10) to non-amplified with the updated 2018 guidelines. Under the 2018 criteria, a total of 259 cases (7.7%) belonged to the uncommon categories (groups 2 to 4), with group 3 being the most frequent (4.6%), followed by group 4 (2.9%) and group 2 (0.2%). Implementation of 2018 guidelines resulted in a significant increase in HER2 non-amplified cases, mainly due to the abolishment of the equivocal FISH group. This has helped resolve the clinical practice dilemma by providing a more definitive HER2 gene status. 相似文献
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《The lancet oncology》2022,23(1):125-137
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《Journal of cystic fibrosis》2022,21(6):1066-1069
Elexacaftor/tezacaftor/ivacaftor (ELX-TEZ-IVA) is a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator shown to improve lung function and reduce sweat chloride in people with Cystic Fibrosis (CF). The only commonly reported dermatologic adverse effect with CFTR modulators including ELX-TEZ-IVA is rash. In this case series, we describe 19 patients who reported new onset or worsening of acne after initiation of this drug to their CF pharmacist or another member of their CF care team. The mechanism and frequency of this adverse effect is unknown. 相似文献