RESUMO
BCL11A encodes a zinc finger protein that is highly expressed in hematopoietic tissues and the brain, and that is known to function as a transcriptional repressor of fetal hemoglobin (HbF). Recently, de novo variants in BCL11A have been reported in individuals with intellectual disability syndrome without epilepsy. In this study, we performed whole-exome sequencing of 302 patients with epileptic encephalopathies (EEs), and identified 2 novel BCL11A variants, c.577delC (p.His193Metfs*3) and c.2351A>C (p.Lys784Thr). Both the patients shared major physical features characteristic of BCL11A-related intellectual disability syndrome, suggesting that characteristic physical features and the persistence of HbF should lead clinicians to suspect EEs caused by BCL11A pathogenic variants. Patient 1, with a frameshift variant, presented with Lennox-Gastaut syndrome, which expands the phenotypic spectrum of BCL11A haploinsufficiency. Patient 2, with a p.Lys784Thr variant, presented with West syndrome followed by drug-resistant focal seizures and more severe developmental disability. These 2 newly described patients contribute to delineating the associated, yet uncertain phenotypic characteristics of BCL11A disease-causing variants.
Assuntos
Encefalopatias/genética , Proteínas de Transporte/genética , Epilepsia/genética , Deficiência Intelectual/genética , Proteínas Nucleares/genética , Adolescente , Encefalopatias/fisiopatologia , Criança , Epilepsia/fisiopatologia , Feminino , Mutação da Fase de Leitura/genética , Humanos , Recém-Nascido , Deficiência Intelectual/fisiopatologia , Síndrome de Lennox-Gastaut/genética , Síndrome de Lennox-Gastaut/fisiopatologia , Masculino , Proteínas Repressoras , Espasmos Infantis/genética , Espasmos Infantis/fisiopatologia , Sequenciamento do ExomaRESUMO
Management of post-transplant complications caused by severe adenoviral infection remains a major therapeutic challenge. A 17-year-old male who had undergone bone marrow transplantation for the treatment of acute lymphoblastic leukemia developed complete anuria following hemorrhagic cystitis 34 days after the transplant procedure. The computed tomogram scan revealed bilateral hydronephrosis, indicating acute renal failure because of obstructive uropathy. The emergency procedure of percutaneous nephrostomy caused massive bleeding in the left kidney, which eventually required a nephrectomy. Adenovirus-positive severe necrotizing tubulointerstitial nephritis was the histopathological diagnosis. Post-transplant acute renal failure because of hydronephrosis, which could be complicated by adenovirus-induced renal parenchymal disease, is of great concern and may cause significant problems with interventional treatment.
Assuntos
Injúria Renal Aguda/etiologia , Infecções por Adenovirus Humanos/complicações , Transplante de Medula Óssea/efeitos adversos , Nefrite Intersticial/complicações , Doenças Urológicas/complicações , Infecções por Adenovirus Humanos/etiologia , Adolescente , Transplante de Medula Óssea/imunologia , Humanos , Hidronefrose/etiologia , Hospedeiro Imunocomprometido , Masculino , Necrose , Nefrite Intersticial/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMO
A rare association of Epstein-Barr virus-associated T- and B-lymphoproliferative disease (EBV(+) T- and EBV(+) B-LPD) in a patient with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is reported. A 26-year-old Japanese female, who had been treated for WHIM syndrome since early childhood, developed hemophagocytic syndrome associated with EBV(+) T-LPD at the lymph nodes and spleen. The disease rapidly resolved in response to prednisolone therapy. However, 6 weeks later, fatal EBV(+) B lymphoma unresponsive to chemotherapy occurred in the intestine and other organs. Caution must be exercised that the patient with WHIM syndrome may be at risk for EBV-LPD.