IDH1 R132C and ERC2 L309I Mutations Contribute to the Development of Maffucci's Syndrome.

Background: Maffucci's syndrome is characterized by the coexistence of multiple enchondromas and soft-tissue hemangiomas. It has been clear that somatic mosaic isocitrate dehydrogenase type 1 (IDH1) or isocitrate dehydrogenase type 2 (IDH2) mutations are associated with Maffucci's syndrome and Ollier disease, but the mechanisms underlying hemangiomas of the Maffucci's syndrome is still obscure. This study aimed to determine the mechanism of hemangiomas in Maffucci's syndrome. Methods: We received a 26-year-old female patient with typical Maffucci's syndrome, and exome sequencing was conducted using DNA from her peripheral blood and enchondroma tissues. Somatic mutations were characterized by a comparative analysis of exome sequences and further confirmed by the sequencing of PCR products derived from original blood and tissue samples. The mutations of an additional 69 patients with Ollier disease were further tested. The functional impacts of these somatic mutations on Maffucci's syndrome, especially the development of hemangiomas, were evaluated. Results: We reported a typical case of Maffucci's syndrome, which was confirmed by both imaging findings and pathology. Through exome sequencing of this patient's DNA samples, we identified an R132C mutation in the isocitrate dehydrogenase type 1 (IDH1) gene and an L309I mutation in the ELKS/RAB6-interacting/CAST family member 2 (ERC2) gene in this patient. Approximately 33.3% of the clones were positive for the IDH1 R132C mutation, and 19.0% of the clones were positive for the ECR2 L309I mutation. The IDH1 R132C mutation was detected in most of the patients with Ollier disease (51/69 patients), and the mean frequency of this mutation was 63.3% in total sequence readouts, but the ECR2 L309I mutation was absent in all of the patients with Ollier disease. In vitro experiments confirmed that the IDH1 R132C mutation promotes chondrocyte proliferation, and the ERC2 L309I mutation enhances angiogenesis. Conclusions: Our results suggest that while IDH1 is a known pathogenic gene in enchondromatosis, ERC2 is a novel gene identified in Maffucci's syndrome. The somatic L309I mutation of ERC2 contributes to the pathogenesis of hypervascularization to facilitate the development of hemangiomas in Maffucci's syndrome. The combination of the IDH1 R132C and ERC2 L309I mutations contributes to the development of Maffucci's syndrome, and these results may enable further research on the pathogenesis of Maffucci's syndrome.

A Participant-assigned Interventional Research of Precesarean Internal Iliac Artery Balloon Catheterization for Managing Intraoperative Hemorrhage of Placenta Previa and Placenta Accreta Spectrum Disorders After Cesarean Section.

Placenta accreta spectrum disorder (PASD) and placenta previa (PP) are two of the most hideous obstetric complications which are usually associated with a history of cesarean section (CS). Moreover, women with PASD, PP and/or a cesarean scarred uterus are more likely to have adverse pregnancy outcomes, including blood transfusion, hysterectomy, pelvic organs damage, postpartum hemorrhage, disseminated intravascular coagulation, multi-organ dysfunction syndrome and even maternal or fetal death. This study aimed to investigate the efficacy of precesarean internal iliac artery balloon catheterization (BC) for managing severe hemorrhage caused by PASD and PP with a history of CS. This participant-assigned interventional study was conducted in Tongji Hospital. We recruited 128 women with suspected PASD, PP and a history of CS. Women in the BC group accepted precesarean BC of bilateral internal iliac arteries before the scheduled cesarean delivery. Women in the control group underwent a conventional cesarean delivery. Intraoperative hemorrhage, transfusion volume, radiation dose, exposure time, complications and neonatal outcomes were discussed. There were significant differences in calculated blood loss (CBL) between BC group and control group (1015.0±144.9 vs. 1467.0±171.0 mL, P=0.04). Precesarean BC could reduce intraoperative red blood cell (RBC) transfusion as compared with control group (799.5±136.1 vs. 1286.0±161.6 mL, P=0.02) and lessen the rate of using blood products (57.1% vs. 76.4%, P=0.02). The incidence of hysterectomy was also lower in BC group than in control group. Postpartum outcomes showed no significant differences between the two groups, except that postoperation hospitalization was longer in BC group than in control group (6.7±0.4 vs. 5.8±0.2 days, P=0.03). Precesarean BC of internal iliac artery is an effective method for managing severe hemorrhage caused by PASD and PP with a cesarean scarred uterus, as it could reduce intraoperative blood loss, lessen intraoperative RBC transfusions and potentially decrease hysterectomies.