ABSTRACT
Skin histology of papules and pustules from 5 men having sex with men with mpox infection showed viral intracytoplasmic cytopathic changes, interface dermatitis, marked inflammatory dermic infiltrate including superficial neutrophils and perivascular and periadnexal deep lymphocytes. Histologic description of mpox lesions improves our understanding about clinical presentations and may have some therapeutic implications.
Subject(s)
Dermatitis , Mpox (monkeypox) , Male , Humans , Disease Outbreaks , Blister , NeutrophilsSubject(s)
HIV Infections , Mpox (monkeypox) , Humans , HIV Infections/complications , Ulcer , PatientsSubject(s)
Glucocorticoids/therapeutic use , Leukemia, Myeloid, Acute/complications , Myelodysplastic Syndromes/complications , Sweet Syndrome/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/immunology , Male , Middle Aged , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/immunology , Recurrence , Retrospective Studies , Risk Factors , Skin/immunology , Skin/pathology , Sweet Syndrome/diagnosis , Sweet Syndrome/drug therapy , Sweet Syndrome/immunology , Symptom Flare Up , Time FactorsABSTRACT
A single missense variant of the TMPO/LAP2α gene, encoding LAP2 proteins, has been associated with cardiomyopathy in two brothers. To further evaluate its role in cardiac muscle, we included TMPO in our cardiomyopathy diagnostic gene panel. A screening of ~5000 patients revealed three novel rare TMPO heterozygous variants in six males diagnosed with hypertrophic or dilated cardiomypathy. We identified in different cellular models that (1) the frameshift variant LAP2α p.(Gly395Glufs*11) induced haploinsufficiency, impeding cell proliferation and/or producing a truncated protein mislocalized in the cytoplasm; (2) the C-ter missense variant LAP2α p.(Ala240Thr) led to a reduced proximity events between LAP2α and the nucleosome binding protein HMGN5; and (3) the LEM-domain missense variant p.(Leu124Phe) decreased both associations of LAP2α/ß with the chromatin-associated protein BAF and inhibition of the E2F1 transcription factor activity which is known to be dependent on Rb, partner of LAP2α. Additionally, the LAP2α expression was lower in the left ventricles of male mice compared to females. In conclusion, our study reveals distinct altered properties of LAP2 induced by these TMPO/LAP2 variants, leading to altered cell proliferation, chromatin structure or gene expression-regulation pathways, and suggests a potential sex-dependent role of LAP2 in myocardial function and disease.
Subject(s)
Cardiomyopathies , Chromosomes , Female , Male , Mice , Animals , Cardiomyopathies/genetics , Chromatin , PhenotypeABSTRACT
This case report describes a 37-year-old man with a 1-week history of a genital nodule that rapidly ulcerated and with concomitant fever 2 days after anal intercourse.