A New Patient with NOCARH Syndrome Due to CDC42 Defect
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LETTER TO EDITOR
A New Patient with NOCARH Syndrome Due to CDC42 Defect Tingyan He 1 & Yanyan Huang 1 & Jiayun Ling 1 & Jun Yang 1 Received: 16 December 2019 / Accepted: 29 April 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
To the editor, CDC42 is a Ras-related GTP-binding protein that plays roles in a variety of biologic activities including cell adhesion, migration, polarization, proliferation, and malignant transformation. Germline pathogenic heterozygous mutations in CDC42 lead to Takenouchi-Kosaki syndrome, presenting with neurodevelopmental delay, distinctive facial features, cardiovascular defects, musculoskeletal anomalies, macrothrombocytopenia, lymphedema, and variable immunodeficiencies. Different from actinopathies with neurological and myologic features, a novel inflammatory syndrome in eight patients due to de novo mutations of CDC42 has been described recently, characterized by neonatal onset of pancytopenia, autoinflammation, rash, and episodes of hemophagocytic lymphohistiocytosis (NOCARH) [1, 2] (Table 1). All these genetic variants affect the C-terminal last five amino acids of CDC42, including c.556C>T (p.R186C), c.563G>A (p.C188Y), and c.576A>C (p.*192C*24) [2]. The p.R186C mutant CD42 fails to interact with RhoGDI/IQGAP1, causing aberrant subcellular localization of CDC42, disruption of certain hematopoietic compartments, and malfunction of NK cells [1]. Herein, we report a Chinese patient with de novo CDC42 mutation, presenting with neonatal onset of rash, pancytopenia, autoinflammation, and an elevated IgE level. This case potentially expands the spectrum of clinical and immunological phenotypes for NOCARH.
Tingyan He and Yanyan Huang contributed equally to this work Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-020-00786-7) contains supplementary material, which is available to authorized users. * Jun Yang [email protected] 1
Department of Rheumatology and Immunology, Shenzhen Children’s hospital, 7019 Yitian Road, Shenzhen 518026, China
The patient was born at term from healthy nonconsanguineous parents without a family history of autoimmune or autoinflammatory disorders, recurrent infections, allergic diseases, or any inherited diseases (Fig. 1a). His elder brother was healthy. From the second day after birth, the patient started to present with erythematous skin lesions in the face, trunk, and limbs (Fig. 1b), in accompanying with recurrent high fever and diarrhea. Laboratory tests showed leukopenia, neutropenia, and thrombocytopenia; increased C-reactive protein (CRP, 58.45 ~ 133.5 mg/l), ferritin (1650 μg/l), and lactate dehydrogenase (LDH, 1244 IU/l) levels. Infection was excluded from extensive microbiological screening negatives, normal cerebrospinal fluid examination (CSF), and unresponsiveness to antibiotics. At the age of 20 days, he was transferred to another hospital for clinical deterioration including transfusion-dependent thrombocytopenia, abdominal distension, chronic diarrhea, and enla
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