ABSTRACT
Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyze the transfer of methyl groups from S-adenosyl-l-methionine to nitrogen atoms on arginine residues. Arginine methylation is involved in multiple biological processes, such as signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation. Currently, 10 patients have been described with mutations in PRMT7. The shared findings include: hypotonia, intellectual disability, short stature, brachydactyly, and mild dysmorphic features. We describe the prenatal, postnatal, and pathological findings in two male sibs homozygote for a mutation in PRMT7. Both had intrauterine growth restriction involving mainly the long bones. In addition, eye tumor was found in the first patient, and nonspecific brain calcifications and a systemic venous anomaly in the second. The pregnancy of the first child was terminated and we describe the autopsy findings. The second child had postnatal growth restriction of prenatal onset, hypotonia, strabismus, sensorineural hearing loss, genitourinary and skeletal involvement, and global developmental delay. He had dysmorphic features that included frontal bossing, upslanting palpebral fissures, small nose with depressed nasal bridge, and pectus excavatum. Our patients provide additional clinical and pathological data and expand the phenotypic manifestations associated with PRMT7 homozygote/compound heterozygote mutations to include brain calcifications and delayed myelination, and congenital orbital tumor.
Subject(s)
Developmental Disabilities/genetics , Intellectual Disability/genetics , Orbital Neoplasms/genetics , Protein-Arginine N-Methyltransferases/genetics , Arginine/genetics , Astrocytoma/genetics , Astrocytoma/physiopathology , Brachydactyly/diagnostic imaging , Brachydactyly/genetics , Brachydactyly/physiopathology , Developmental Disabilities/diagnostic imaging , Developmental Disabilities/physiopathology , Female , Fetal Growth Retardation/genetics , Fetal Growth Retardation/physiopathology , Humans , Infant , Infant, Newborn , Intellectual Disability/diagnostic imaging , Intellectual Disability/physiopathology , Male , Methylation , Muscle Hypotonia/diagnostic imaging , Muscle Hypotonia/genetics , Muscle Hypotonia/physiopathology , Mutation/genetics , Orbital Neoplasms/diagnostic imaging , Orbital Neoplasms/physiopathology , PregnancyABSTRACT
This paper presents a numerical analysis of the hemodynamics in an abdominal aorta (AA) with an aneurysm repaired by a stent graft (SG) system using the chimney technique. Computational fluid dynamics (CFD) simulations were conducted in a model of an AA repaired with a chimney stent graft (CSG) inserted into a renal artery parallel to an aortic SG and a model of a healthy AA. Comparing the simulation results of these two cases suggests that the presence of the CSG in the AA causes changes in average wall shear stress (WSS), potentially damaging recirculation zones, and additional changes in flow patterns.
Subject(s)
Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Hemodynamics , Humans , Models, Cardiovascular , Stents , Treatment OutcomeABSTRACT
Aberrant activation of the canonical Wnt signal transduction pathway is involved in a large number of human diseases. ß-catenin, the key effector protein of the canonical Wnt pathway, functions in the nucleus with T-cell factor/lymphoid enhancer factor (TCF/LEF) to activate expression of Wnt target genes. Here we show that members of the 14-3-3 protein family bind disheveled-2 (Dvl-2) and glycogen synthase-3ß (GSK-3ß) to attenuate the interaction between GSK-3ß and ß-catenin. Importantly, 14-3-3 and ß-catenin form "bleb-like" structures and are secreted via extracellular vesicles to induce Wnt signaling activity in target cells. Our data suggest a novel way of transducing the oncogenic Wnt signal in which ß-catenin is regulated by 14-3-3ζ through the formation of "oncosomes" that contain both the 14-3-3 and ß-catenin proteins.
