Background: Primary desminopathies are caused by desmin gene [DES (MIM*125660)] mutations. The clinical spectrum includes pure myopathies, cardiomuscular diseases and cardiomyopathies. Patients with restrictive cardiomyopathy (RCM) plus atrioventricular block (AVB) due to DES defects are frequently unrecognized unless desmin accumulation is specifically investigated in endomyocardial biopsy (EMB) by ultrastructural study.
Aims: To describe a cardiological phenotype characterized by RCM plus AVB due to desmin accumulation caused by DES defects.
Methods And Results: Desmin accumulation was diagnosed by means of ultrastructural and immunocytochemical studies of EMB in four unrelated probands with RCM and AVB. Candidate genes [DES and alphaB-crystallin (CRYAB)] were screened using sequence analysis. Four DES gene mutations were identified: three new (R16C, T453I and a 10 bp deletion at the exon-intron boundary of exon 3 disrupting the donor splice site) and one known (R406W). The disease was autosomal dominant in two families, recessive in one and associated with a de novo mutation in one. The mutations cosegregated with phenotype in all patients. CRYAB gene screening was negative.
Conclusions: A cardiac phenotype characterized by RCM and AVB caused by desmin accumulation is associated with DES mutations. Although the mutations affected different domains, the cardiac phenotype was identical.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.ejheart.2005.11.003 | DOI Listing |
J Muscle Res Cell Motil
December 2024
West China Developmental & Stem Cell Biology Institute, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Desmin and Vimentin are major intermediate filaments at the Z-disc and play significant roles in sarcomere architecture and signaling transduction. Abnormal expression of sarcomeric Desmin and Vimentin (SDV) results in severe dysfunctions of striated muscles. In this study, it was found that paired Numb family proteins (NFPs), including Numb and its homolog Numblike, determined the range for the recruitment of SDV to the primitive Z-disc.
View Article and Find Full Text PDFFront Pharmacol
November 2024
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
Introduction And Aims: Vitamin D has an immunomodulatory property influencing the activity of NKT cells. We aimed to study the impact of osteopontin (OPN), a key driver of fibrosis, on NKT cells' vitamin D receptor (VDR) and activity alterations.
Methods: Liver fibrosis was induced in BALB/C mice with carbon-tetrachloride (CCl) for 8 weeks with either vitamin D [100 ng/kg] or InVivoMAb anti-mouse OPN [100 μg/kg] 2X/week started at week-4 of CCl The liver injury profile of serum ALT, AST, and inflammatory cytokines were evaluated.
Naunyn Schmiedebergs Arch Pharmacol
October 2024
Pharmacology and Toxicology Department, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Metabolic syndrome is associated with vitamin D3 deficiency. This work aims to examine the efficacy of vitamin D3 in inhibiting MetS-induced myopathy and to determine whether the beneficial effects of vitamin D3 are mediated by the inhibition of dipeptidyl peptidase-4 (DPP-4). An in silico study investigated the potential effectiveness of vitamin D3 on the inhibition of the DPP-4 enzyme.
View Article and Find Full Text PDFBackground: Crystalloid storage histiocytosis (CSH) is a rare clinical condition characterized by abnormally high numbers of histiocytes with a large accumulation of crystalline immunoglobulins. Due to its relative rarity, clinical diagnosis of it is frequently incomplete or incorrect. We report a case with pulmonary crystal-storing histiocytosis that was mistakenly identified as lung carcinoma.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!