RESUMEN
OBJECTIVE@#To delineate the clinical feature and genetic basis of four patients with congenital neutropenia.@*METHODS@#All patients were subjected to whole exome sequencing (WES). Suspected variants were verified by Sanger sequencing.@*RESULTS@#The patients (two boys and two girls), aged 7 to 15 months, suffered from neutropenia and recurrent infections. Bone marrow smears showed a significant decrease in the proportion of rod-shaped and lobulated granulocytes, which suggested impaired development and maturation of bone marrow neutrophils. WES has discovered heterozygous variants (c.496G>A, c.58C>G, c.391G>A and IVS1+5T>A) of the ELANE gene in the patients. Among these, c.58C>G and IVS1+5T>A were unreported previously. Follow up revealed patients 1 and 3 had periodic neutropenia, while patients 2 and 4 had severe congenital neutropenia. After attaining the definite diagnosis, the patients were treated symptomatically.@*CONCLUSION@#The main clinical feature of congenital neutropenia is refractory recurrent bacterial infections, for which mutations of the ELANE gene are a common cause. Two novel pathogenic ELANE variants have been discovered in this study.
Asunto(s)
Femenino , Humanos , Lactante , Masculino , Síndromes Congénitos de Insuficiencia de la Médula Ósea/genética , Pruebas Genéticas , Elastasa de Leucocito/genética , Mutación , Neutropenia/genéticaRESUMEN
Severe congenital neutropenia (SCN) is a heterogeneous group of disorders with a defect in granulopoiesis causing marked neutropenia and severe bacterial infections. A 17-month-old girl (patient 1) was admitted due to cervical lymphadenitis caused by methicillin-resistant Staphylococcus aureus, with neutropenia. She had Pseudomonas aeruginosa sepsis and peritonitis with perforated appendicitis at 8-month of age. Her sister, a 37-month-old girl (patient 2), had recurrent stomatitis with profound neutropenia, and her mother, a 32-yr-old woman (patient 3), had had recurrent stomatitis until her early 20s with neutropenia. We found an ELANE gene mutation (c.597+1G > A) from them in direct DNA sequencing analysis. Patients 1 and 2 did not respond to granulocyte colony stimulating factor and patient 1 was treated with prolonged antibiotics and excision. We demonstrated inherited SCN cases showing different severity even with the same mutation of the ELANE gene in a family.
Asunto(s)
Adulto , Preescolar , Femenino , Humanos , Lactante , Análisis Mutacional de ADN , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Elastasa de Leucocito/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Mutación/genética , Neutropenia/congénito , Linaje , Fenotipo , Polimorfismo de Nucleótido Simple , Recurrencia , Infecciones Estafilocócicas/diagnóstico , Estomatitis/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
Severe congenital neutropenia is a heterozygous group of bone marrow failure syndromes that cause lifelong infections. Mutation of the ELANE gene encoding human neutrophil elastase is the most common genetic alteration. A Korean female pediatric patient was admitted because of recurrent cervical lymphadenitis without abscess formation. She had a past history of omphalitis and isolated neutropenia at birth. The peripheral blood showed a markedly decreased absolute neutrophil count, and the bone marrow findings revealed maturation arrest of myeloid precursors at the promyelocyte to myelocyte stage. Her direct DNA sequencing analysis demonstrated an ELANE gene mutation (c.607G > C; p.Gly203Arg), but her parents were negative for it. She showed only transient response after subcutaneous 15 microg/kg/day of granulocyte colony stimulating factor administration for six consecutive days. During the follow-up observation period, she suffered from subsequent seven febrile illnesses including urinary tract infection, septicemia, and cellulitis.
Asunto(s)
Femenino , Humanos , Lactante , Infecciones Bacterianas , Secuencia de Bases , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Recuento de Leucocitos , Elastasa de Leucocito/genética , Linfadenitis , Neutropenia/sangre , Neutrófilos , Mutación Puntual , República de Corea , Análisis de Secuencia de ADNRESUMEN
Congenital neutropenia is a rare hematopoietic disease, which occurs sporadically or as an auto-somal dominant inherited disorder. Pathogenesis of congenital neutropenia can now be attributed to mutations of the ELA2 gene encoding neutrophil elastase. A child with severe congenital neutropenia with a heterozygous mutation G1887A in exon 2 of ELA2 gene is reported.
Asunto(s)
Análisis Mutacional de ADN , Electroforesis en Gel Bidimensional , Femenino , Heterocigoto , Humanos , Elastasa de Leucocito/genética , Neutropenia/congénitoRESUMEN
Severe chronic neutropenia (SCN) is a very rare disease with around 650 people worldwide known to have the condition. SCN is a serous condition with a considerable morbidity and mortality if not treated. We hereby report a case of SCN which had repeated admissions to the hospital with severe neutropenia and high grade fever. We also review the literature elucidating some of the mechanisms and consequences of SCN ( e.g: the neutrophil elastase gene mutations and the risk of progression to myelodysplasia and acute leukemia) and the role of granulocyte-colony stimulating factor.