RESUMO
CDC42 (cell division cycle protein 42) belongs to the Rho GTPase family that is known to control the signaling axis that regulates several cellular functions, including cell cycle progression, migration, and proliferation. However, the functional characterization of the CDC42 gene in mammalian physiology remains largely unclear. Here, we report the genetic and functional characterization of a non-consanguineous Saudi family with a single affected individual. Clinical examinations revealed poor wound healing, heterotopia of the brain, pancytopenia, and recurrent infections. Whole exome sequencing revealed a de novo missense variant (c.101C > A, p.Pro34Gln) in the CDC42 gene. The functional assays revealed a substantial reduction in the growth and motility of the patient cells as compared to the normal cells control. Homology three-dimensional (3-D) modeling of CDC42 revealed that the Pro34 is important for the proper protein secondary structure. In conclusion, we report a candidate disease-causing variant, which requires further confirmation for the etiology of CDC42 pathogenesis. This represents the first case from the Saudi population. The current study adds to the spectrum of mutations in the CDC42 gene that might help in genetic counseling and contributes to the CDC42-related genetic and functional characterization. However, further studies into the molecular mechanisms that are involved are needed in order to determine the role of the CDC42 gene associated with aberrant cell migration and immune response.
Assuntos
Encéfalo/anormalidades , Estudos de Associação Genética , Predisposição Genética para Doença , Pancitopenia/genética , Reinfecção/etiologia , Cicatrização/genética , Proteína cdc42 de Ligação ao GTP/deficiência , Biópsia , Encéfalo/diagnóstico por imagem , Biologia Computacional/métodos , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética/métodos , Humanos , Imageamento por Ressonância Magnética , Modelos Moleculares , Mutação , Pancitopenia/diagnóstico , Linhagem , Conformação Proteica , Reinfecção/diagnóstico , Relação Estrutura-Atividade , Sequenciamento do Exoma , Adulto Jovem , Proteína cdc42 de Ligação ao GTP/químicaRESUMO
Polyarteritis nodosa (PAN) is a rare type of childhood vasculitis. We report the case of a 10-year-old boy who was referred to our hospital following an appendicectomy with fever, abdominal pain, vomiting, diarrhoea, weight loss, joint pains and skin rash. Shortly after admission, he developed peritonitis, and an emergency laparotomy revealed ischaemia of the jejunum which required partial resection. Histologic examination of the resected bowel showed features consistent with PAN. He was treated with steroids and cyclophosphamide. Nineteen months later, he is asymptomatic and thriving. PAN should be included in the differential diagnosis if a child with constitutional symptoms also has gastrointestinal complaints or develops an acute abdomen.
