RESUMO
Isolated congenital diaphragmatic hernia is often a sporadic event with a low recurrence risk. However, underlying genetic etiologies, such as chromosome anomalies or single gene disorders, are identified in a small number of individuals. We describe two fetuses with a unique pattern of multiple congenital anomalies, including diaphragmatic hernia, short bowel and asplenia, born to first-cousin parents. Whole exome sequencing showed that both were homozygous for a missense variant, c.950A>C, predicting p.Asp317Ala, in the H.20-Like Homeobox 1 (HLX1) gene. HLX is a homeobox transcription factor gene which is relatively conserved across species. Hlx homozygous null mice have a short bowel and reduced muscle cells in the diaphragm, closely resembling the anomalies in the two fetuses and we therefore suggest that the HLX mutation in this family could explain the fetal findings.
Assuntos
Hérnias Diafragmáticas Congênitas/genética , Síndrome de Heterotaxia/genética , Proteínas de Homeodomínio/genética , Síndrome do Intestino Curto/genética , Fatores de Transcrição/genética , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/fisiopatologia , Animais , Anormalidades do Sistema Digestório/genética , Anormalidades do Sistema Digestório/fisiopatologia , Predisposição Genética para Doença , Hérnias Diafragmáticas Congênitas/fisiopatologia , Síndrome de Heterotaxia/fisiopatologia , Humanos , Camundongos , Mutação , Análise de Sequência de DNA , Síndrome do Intestino Curto/fisiopatologia , Sequenciamento do ExomaAssuntos
Listeriose/complicações , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Feminino , Gentamicinas/uso terapêutico , Humanos , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Recém-Nascido/microbiologia , Transmissão Vertical de Doenças Infecciosas , Listeriose/transmissão , Masculino , Gravidez , Complicações Infecciosas na Gravidez/diagnósticoAssuntos
Anormalidades Múltiplas/genética , Rim/anormalidades , Síndrome de Smith-Lemli-Opitz/diagnóstico , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/patologia , Aborto Induzido , Feminino , Deformidades Congênitas do Pé/genética , Deformidades Congênitas do Pé/patologia , Humanos , Oligo-Hidrâmnio/diagnóstico , Polidactilia/genética , Polidactilia/patologia , Gravidez , Sindactilia/genética , Sindactilia/patologia , UltrassonografiaRESUMO
BACKGROUND: Varicella Zoster virus (VZV) infection is potentially very serious in bone marrow transplant recipients, and may manifest as a disseminated visceral infection. This condition is generally accompanied by a vesicular rash. OBJECTIVES: We review here a case of fulminant fatal disseminated VZV infection, not accompanied by skin involvement, and the laboratory approaches currently available to diagnose this disease. STUDY DESIGN: Post mortem tissue samples were subjected to histopathological examination, and tested for herpesviruses by electron microscopy and PCR. RESULTS: Intranuclear inclusions were noted by histological examination in the lungs, liver, kidneys and bone marrow. Particles with a herpesvirus morphology were visualized in liver tissue. VZV DNA was detected in liver and bone marrow by PCR followed by sequencing of the amplicons. Viremia was documented by retrospective testing of the serum by PCR. CONCLUSIONS: A disseminated VZV infection which proved rapidly fatal was demonstrated in a case without skin manifestations. This rare presentation of VZV infection is potentially underdiagnosed. Testing for VZV viremia by PCR can at the very least suggest the diagnosis although whether plasma-associated viremia is truly pathognomonic of visceral disseminated infection remains to be established.
