ABSTRACT
The gene IL6ST encodes GP130, the common signal transducer of the IL-6 cytokine family consisting of 10 cytokines. Previous studies have identified cytokine-selective IL6ST defects that preserve LIF signaling. We describe three unrelated families with at least five affected individuals who presented with lethal Stüve-Wiedemann-like syndrome characterized by skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. We identified essential loss-of-function variants in IL6ST (a homozygous nonsense variant and a homozygous intronic splice variant with exon skipping). Functional tests showed absent cellular responses to GP130-dependent cytokines including IL-6, IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF). Genetic reconstitution of GP130 by lentiviral transduction in patient-derived cells reversed the signaling defect. This study identifies a new genetic syndrome caused by the complete lack of signaling of a whole family of GP130-dependent cytokines in humans and highlights the importance of the LIF signaling pathway in pre- and perinatal development.
Subject(s)
Cytokine Receptor gp130/metabolism , Exostoses, Multiple Hereditary/metabolism , Osteochondrodysplasias/metabolism , Signal Transduction/physiology , Antigens, CD/metabolism , Cells, Cultured , HEK293 Cells , Humans , Interleukin-11/metabolism , Interleukin-6/metabolism , Leukemia Inhibitory Factor/metabolism , Oncostatin M/metabolism , Receptors, Cytokine/metabolismABSTRACT
Preterm infants are highly susceptible to injuries following necessary and often life-saving medical interventions. Esophageal perforation is a rare, yet serious complication that can be caused by aerodigestive tract suction, endotracheal intubation, or nasogastric tube placement. We present the case of a neonate born at 23 weeks plus three days of gestation with chest radiography showing malposition of the nasogastric feeding tube and massive right-sided effusion of Iopamidol in the pleural cavity due to esophageal perforation. In addition, the article summarizes common signs and symptoms associated with esophageal perforation in infants and discusses diagnostic approaches.
ABSTRACT
A 4 ½-year-old female was diagnosed with ovarian juvenile granulosa cell tumor stage IA. After complete tumor resection she received 4 courses of chemotherapy due to unfavorable histopathologic features (high mitotic index, high microvessel density, blood vessel invasion). One year after diagnosis, she experienced paraaortic lymph node relapse treated with surgery, local radiotherapy, and conventional and high-dose chemotherapy. A second, paratracheal lymph node relapse 7 months later necessitated surgical removal and radiotherapy. Subsequently an adjuvant antiangiogenesis-based treatment including paclitaxel, bevacizumab, thalidomide, and pegylated interferon was initiated and continued for 2 years. The female is now in third complete remission 6 years after second relapse.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Granulosa Cell Tumor/secondary , Ovarian Neoplasms/drug therapy , Salvage Therapy , Child, Preschool , Female , Granulosa Cell Tumor/therapy , Humans , Lymph Node Excision , Lymphatic Irradiation , Lymphatic Metastasis/radiotherapy , Neoplasm Staging , Neovascularization, Pathologic/drug therapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Ovariectomy , Remission InductionABSTRACT
Intrauterine ovarian torsion is a rare event, but it is a possible cause for unilateral ovarian aplasia. Most commonly the ovary undergoes autolysis after torsion so that no tissue or remnants can be discovered on the involved side. We report a rare case of unilateral intrauterine torsion followed by autoamputation and abdominal reimplantation resulting in an intra-abdominal complex cystic mass with a review of the literature.
