RESUMEN
Dysfunction of the gonadotropin-releasing hormone (GnRH) axis causes a range of reproductive phenotypes resulting from defects in the specification, migration and/or function of GnRH neurons. To identify additional molecular components of this system, we initiated a systematic genetic interrogation of families with isolated GnRH deficiency (IGD). Here, we report 13 families (12 autosomal dominant and one autosomal recessive) with an anosmic form of IGD (Kallmann syndrome) with loss-of-function mutations in TCF12, a locus also known to cause syndromic and non-syndromic craniosynostosis. We show that loss of tcf12 in zebrafish larvae perturbs GnRH neuronal patterning with concomitant attenuation of the orthologous expression of tcf3a/b, encoding a binding partner of TCF12, and stub1, a gene that is both mutated in other syndromic forms of IGD and maps to a TCF12 affinity network. Finally, we report that restored STUB1 mRNA rescues loss of tcf12 in vivo. Our data extend the mutational landscape of IGD, highlight the genetic links between craniofacial patterning and GnRH dysfunction and begin to assemble the functional network that regulates the development of the GnRH axis.
Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Hormona Liberadora de Gonadotropina/genética , Síndrome de Kallmann/genética , Ubiquitina-Proteína Ligasas/genética , Proteínas de Pez Cebra/genética , Adulto , Anciano , Animales , Modelos Animales de Enfermedad , Femenino , Genes Dominantes/genética , Hormona Liberadora de Gonadotropina/deficiencia , Haploinsuficiencia/genética , Humanos , Síndrome de Kallmann/patología , Masculino , Persona de Mediana Edad , Mutación/genética , Neuronas/metabolismo , Neuronas/patología , Fenotipo , Pez Cebra/genéticaRESUMEN
We report the unusual presentation of coarctation of the aorta with facial nerve palsy in an infant and a child. The facial nerve palsy and hypertension resolved spontaneously after relief of the aortic coarctation. Our two cases are the first reports of unidentified coarctation of the aorta presenting as facial nerve palsy, with the infant being the youngest to be reported.
RESUMEN
Diaphragmatic herniation following blunt injuries is uncommon in children. We present a case report of a child presenting with a diaphragmatic hernia following a trivial injury leading to mediastinal shift and circulatory compromise resulting in a electromechanical dissociation cardiac arrest.
