RESUMEN
Goldenhar syndrome or oculo-auriculo-vertebral spectrum (OAVS) is a complex developmental disorder characterized by asymmetric ear anomalies, hemifacial microsomia, ocular and vertebral defects. We aimed at identifying and characterizing a new gene associated with OAVS. Two affected brothers with OAVS were analyzed by exome sequencing that revealed a missense variant (p.(Asn358Ser)) in the EYA3 gene. EYA3 screening was then performed in 122 OAVS patients that identified the same variant in one individual from an unrelated family. Segregation assessment in both families showed incomplete penetrance and variable expressivity. We investigated this variant in cellular models to determine its pathogenicity and demonstrated an increased half-life of the mutated protein without impact on its ability to dephosphorylate H2AFX following DNA repair pathway induction. Proteomics performed on this cellular model revealed four significantly predicted upstream regulators which are PPARGC1B, YAP1, NFE2L2 and MYC. Moreover, eya3 knocked-down zebrafish embryos developed specific craniofacial abnormalities corroborating previous animal models and supporting its involvement in the OAVS. Additionally, EYA3 gene expression was deregulated in vitro by retinoic acid exposure. EYA3 is the second recurrent gene identified to be associated with OAVS. Moreover, based on protein interactions and related diseases, we suggest the DNA repair as a key molecular pathway involved in craniofacial development.
Asunto(s)
Reparación del ADN , Proteínas de Unión al ADN/genética , Síndrome de Goldenhar/genética , Mutación Missense , Proteínas Tirosina Fosfatasas/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Secuencia de Aminoácidos , Animales , Niño , Preescolar , Proteínas de Unión al ADN/deficiencia , Embrión no Mamífero , Femenino , Regulación de la Expresión Génica , Síndrome de Goldenhar/metabolismo , Síndrome de Goldenhar/patología , Histonas/genética , Histonas/metabolismo , Humanos , Masculino , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Linaje , Penetrancia , Proteínas Tirosina Fosfatasas/deficiencia , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Hermanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Secuenciación del Exoma , Proteínas Señalizadoras YAP , Pez Cebra/embriología , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
A novel duplication of Xp is described. A 20-year-old man had minor anomalies ichthyosis, congenital heart defect, varicose veins, and hypogonadotropic hypogonadism. He had an interstitial duplication of approximately 2.8 Mb from chromosome region Xp22.31p22.2. His similarly affected brother and asymptomatic mother were shown to carry the same duplication. Knowledge about this duplication and its resultant phenotype will add to our understanding of the role of X chromosome duplications.
Asunto(s)
Duplicación Cromosómica , Cromosomas Humanos X , Adulto , Femenino , Humanos , Masculino , Linaje , FenotipoRESUMEN
Profile of children attending in a Pediatric Emergency Unit of an urban teaching hospital over a period of one year was analyzed. The total number of patients seen between September 1999 to August 2000 was 9205; there was a prepondence of boys (73%). The maximum number of patients were seen in the monsoon month of July and August. About half (52.5%) of the patients were infants. Fever (29.5%), breathing difficulty (17.4%) and diarrhea (14.5%) were the most common presenting symptoms. Respiratory and gastrointestinal illnesses were the two commonest pediatric emergencies. About 2% (n-198) patients died within 24 hours of hospitalization; 42.3% deaths were in the age group of 0-28 days. Sepsis was the most common diagnosis in patients who died. This information may help in planning and development of a Pediatric Emergency unit and prioritizing residents, training.
Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitales de Enseñanza/estadística & datos numéricos , Hospitales Urbanos/estadística & datos numéricos , Pediatría/estadística & datos numéricos , Accidentes/estadística & datos numéricos , Distribución por Edad , Niño , Preescolar , Femenino , Fiebre/epidemiología , Enfermedades Gastrointestinales/epidemiología , Humanos , India/epidemiología , Lactante , Recién Nacido , Enfermedades del Recién Nacido/epidemiología , Masculino , Enfermedades del Sistema Nervioso/epidemiología , Evaluación de Resultado en la Atención de Salud , Enfermedades Respiratorias/epidemiología , Estudios Retrospectivos , Estaciones del Año , Distribución por Sexo , Tasa de Supervivencia , Heridas y Lesiones/epidemiologíaAsunto(s)
Infecciones por Chlamydiaceae , Neumonía Bacteriana/microbiología , Neumonía por Mycoplasma , Adolescente , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Niño , Infecciones por Chlamydiaceae/diagnóstico , Infecciones por Chlamydiaceae/tratamiento farmacológico , Infecciones por Chlamydiaceae/microbiología , Chlamydophila pneumoniae , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Lactante , Pruebas de Fijación de Látex , Legionella , Mycoplasma pneumoniae , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/tratamiento farmacológico , Neumonía por Mycoplasma/diagnóstico , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/microbiología , Reacción en Cadena de la Polimerasa/métodosRESUMEN
Brucellosis is a rare disease in children. Lung involvement is an uncommon presentation of brucellosis. The authors are presenting a child with brucellosis, who presented with predominant pulmonary involvement. It was an eight-year-old child who was referred to us a case of non-resolving pneumonia. Brucella agglutination test was suggestive of brucellosis. He responded to the combination of doxycycline and rifampicin.
RESUMEN
Brucellosis is a rare disease in children. Lung involvement is an uncommon presentation of brucellosis. The authors are presenting a child with brucellosis, who presented with predominant pulmonary involvement. It was an eight-year-old child who was referred to us a case of non-resolving pneumonia. Brucella agglutination test was suggestive of brucellosis. He responded to the combination of doxycycline and rifampicin.
Asunto(s)
Brucelosis/complicaciones , Neumonía/microbiología , Pruebas de Aglutinación , Brucelosis/diagnóstico , Brucelosis/tratamiento farmacológico , Niño , Humanos , Masculino , Neumonía/tratamiento farmacológicoRESUMEN
A case of muscular hypertrophy in a hypothyroid 12-year-old male child, known as Kocher Debre Semelaigne syndrome, is reported with review of the relevant literature. The patient responded well to l-thyroxine therapy.