People with HIV (PWH) and mycobacterial infections can develop immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy. The pathophysiology of mycobacterial-IRIS overlaps with primary hemophagocytic lymphohistiocytosis (pHLH). To assess possible genetic predisposition to IRIS, protein-altering variants in genes associated with HLH were evaluated in 82 PWH and mycobacterial infections who developed IRIS (n = 56) or did not develop IRIS (n = 26). Protein-altering variants in cytotoxicity genes were found in 23.2% of IRIS patients compared to only 3.8% of those without IRIS. These findings suggest a possible genetic component in the risk of mycobacterial IRIS in PWH. Clinical Trials Registration. NCT00286767, NCT02147405.
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http://dx.doi.org/10.1093/infdis/jiad059 | DOI Listing |
Cephalalgia
January 2025
Department of Biomedicine, Health Aarhus University, Aarhus, Denmark.
Background: Familial hemiplegic migraine (FHM) types 1-3 are associated with protein-altering genetic variants in , and , respectively. These genes have also been linked to epilepsy. Previous studies primarily focused on phenotypes, examining genetic variants in individuals with characteristic FHM symptoms.
View Article and Find Full Text PDFJHEP Rep
January 2025
The Institute for Translational Medicine and Therapeutics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Background & Aim: An unbiased genome-first approach can expand the molecular understanding of specific genes in disease-agnostic biobanks for deeper phenotyping. represents a good candidate for this approach due to its known association with steatotic liver disease (SLD).
Methods: We screened participants with whole-exome sequences in the Penn Medicine Biobank (PMBB, n >40,000) and the UK Biobank (UKB, n >200,000) for protein-altering variants in and evaluated their association with liver phenotypes and clinical outcomes.
Brain
December 2024
Department of Neurosurgery, Massachusetts General Hospital & Harvard Medical School, Boston, MA 02114, USA.
Congenital hydrocephalus (CH), characterized by cerebral ventriculomegaly (CV), is among the most common and least understood pediatric neurosurgical disorders. We have identified in the largest-assembled CV cohort (>2,697 parent-proband trios) an exome-wide significant enrichment of protein-altering de novo variants (DNVs) in LDB1 (p = 1.11 x 10-15).
View Article and Find Full Text PDFHypertension
December 2024
Department of Rheumatology, Guangzhou First People's Hospital, Guangzhou Medical University, China. (S.X., Simin Wen, X.Z., Shifeng Wen, C.D., G.R.).
Background: Circulating proteins in blood are involved in various physiological processes, but their contributions to blood pressure regulation remain partially understood. In traditional observational studies, identifying circulating proteins causally associated with blood pressure is challenging because of potentially unmeasured confounding and possible reverse causality.
Methods: Two-sample Mendelian randomization analyses were conducted to estimate the causal effects of 2270 circulating proteins (data sourced from 8 genome-wide association studies) on diastolic blood pressure, systolic blood pressure, and pulse pressure.
medRxiv
November 2024
College of Dentistry and Dental Clinics, University of Iowa, Iowa City, IA, 52240.
Background: Disturbances in the intricate processes that control craniofacial morphogenesis can result in birth defects, most common of which are orofacial clefts (OFCs). Nonsyndromic cleft lip (nsCL), one of the phenotypic forms amongst OFCs, has a non-random laterality presentation with the left side being affected twice as often compared to the right side. This study investigates the etiology of nsCL and the factors contributing to its laterality using a pair of monozygotic twins with mirror-image cleft lip.
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