Cdc42. 4,5 In our study, the doubly lipidated R186C Cdc42 mutant was retained in the Golgi (see Fig E4 , B). This impaired its plasma membrane anchoring and resulted in actin polymerization defects and hyperactivation of NF-kB signaling.In conclusion, our study identifies a strong link between impaired cytosol/membrane cycling of Cdc42 resulting from abnormal double lipidation, partial defects in actin polymerization, and hyperactivation of NF-kB signaling, which can explain the pathophysiology of the disease. More broadly, our findings are consistent with reports in the literature that link inflammation with actin turnover 6 and membrane targeting of Rho GTPases. [7][8][9] Thus, further investigation of the various consequences of CDC42 mutations are required because these mutations arise in a broad spectrum of clinical phenotypes. Ultimately, it offers the possibility of designing specific therapeutic targeting of this pathway that is newly involved in autoinflammatory diseases.

Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of coronavirus disease 2019 (COVID-19) in children, which is increasingly being reported worldwide. Here we report the first case series of 7 children diagnosed with MIS-C in Qatar. Methods Clinical features and outcomes of COVID-19 positive patients admitted to Sidra Medicine, Qatar from June to October 2020, who met the WHO case definition for MIS-C were reviewed. Results The mean age in our case series was 5.6 years, of which 71.4% were males. All patients were previously healthy but had a history of COVID-19 infection. Fever, rash, vomiting and abdominal pain were the most common symptoms (70–100%). The average hospitalization was 12.9 days with no case fatalities. Laboratory findings included lymphopenia and thrombocytopenia in most patients, as well as evidence of coagulopathy and elevated inflammatory markers such as C-reactive protein, ferritin and procalcitonin. Many patients (71.4%) required inotropic support in intensive care, while only one required respiratory support. Although all patients had elevated cardiac biomarkers, cardiovascular involvement was observed in 42.9% of patients with one patient developing a giant coronary aneurysm. All patients received intravenous immunoglobulin (IVIG) and 86% of patients received corticosteroids, with two patients requiring treatment with IL-1 inhibitors. Conclusions Our report is one of the first reports on MIS-C from Asia. Although clinical features and outcomes are not significantly different from those reported elsewhere, lack of case fatalities in our cohort may indicate that early recognition and prompt medical attention is necessary for a favorable outcome in MIS-C.

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of coronavirus disease 2019 (COVID-19) in children, which is increasingly being reported worldwide. Here we report the first case series of 7 children diagnosed with MIS-C in Qatar. Methods: Clinical features and outcomes of COVID-19 positive patients admitted to Sidra Medicine, Qatar from June to October 2020, who met the WHO case definition for MIS-C were reviewed.Results: The mean age in our case series was 5.6 years, of which 71.4% were males. All patients were previously healthy but had a history of COVID-19 infection. Fever, rash, vomiting and abdominal pain were the most common symptoms (70%-100%). The average hospitalization was 12.9 days with no case fatalities. Laboratory findings included lymphopenia and thrombocytopenia in most patients, as well as evidence of coagulopathy and elevated inflammatory markers such as C-reactive protein, ferritin and procalcitonin. Many patients (71.4%) required inotropic support in intensive care, while only one required respiratory support. Although all patients had elevated cardiac biomarkers, cardiovascular involvement was observed in 42.9% of patients with one patient developing a giant coronary aneurysm. All patients received intravenous immunoglobulin (IVIG) and 86% of patients received corticosteroids, with two patients requiring treatment with IL-1 inhibitors.Conclusions: Our report is one of the first reports on MIS-C from Asia. Although clinical features and outcomes are not significantly different from those reported elsewhere, lack of case fatalities in our cohort may indicate that early recognition and prompt medical attention is necessary for a favorable outcome in MIS-C.

The patient, a 14-year-old boy with type 1 Pfeiffer syndrome and a 2-month history of pain in the fourth finger of his left hand, was referred to the rheumatology clinic. The patient presented at birth with craniosynostosis, hypertelorism, and brachydactyly. The geneticists diagnosed Pfeiffer syndrome, and gene testing confirmed a mutation in fibroblast growth factor receptor 1. His clinical history and disease course included hearing loss, initial speech delay (now resolved), dental problems, and malocclusion. In addition to his symptoms of finger pain, he also had intermittent subluxation of his left elbow and both shoulders due to congenital dislocations. Excluding joint pain, the patient denied any other symptoms of inflammatory arthritis. There was no family history of rheumatoid arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, or psoriasis. The musculoskeletal physical examination was remarkable for short broad fingers and toes, decreased range of motion in both the first and second digits, and decreased range of motion in both elbows and shoulders. Radiographs of two views of the hands and wrists showed partial fusion at the first interphalangeal joints bilaterally and the second proximal interphalangeal (PIP) joint of the left hand. The second PIP joint of the right hand was completely fused. The proximal phalanges of the thumb and the middle phalanges of the second and fourth fingers were shortened bilaterally. Both thumbs were radially deviated. The metacarpal heads of both hands also appeared slightly diminutive. There was widening at the distal radioulnar joints, with the ulna appearing abnormally rotated on the frontal view bilaterally, which indicates instability at the radioulnar joint. Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that affects 1 in 100,000 persons. The syndrome is a result of mutations in fibroblast growth factor receptors 1 or 2 leading to gain-of-function altered cell differentiation, including bone cells. There is no association with an inflammatory or autoimmune mechanism. Musculoskeletal involvement in Pfeiffer syndrome is commonly associated with craniosynostosis, maxillary hypoplasia, broad and deviated thumbs and great toes, and partial syndactyly of the hands and feet in addition to joint fusion and ankylosis of small and large joints. The diagnosis of Pfeiffer syndrome is essentially clinical, but radiologic exploration can confirm the associated skeletal abnormalities (1-3). This patient was referred to the rheumatology clinic in order to rule out arthritis. Clinical examination did not reveal the typical findings of inflammatory arthritis but only the musculoskeletal findings described above. Although radiology provided no explanation for the pain in the fourth finger of his left hand, this digit may be in the early stages and a new site for bone formation and ultimate fusion. Serial radiographs can be helpful to document disease progression. Because the process is noninflammatory in nature, magnetic resonance imaging is not indi...