RESUMEN
Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function.
Asunto(s)
Cilios/genética , Síndrome de Kartagener/genética , Proteínas/genética , Sistema Respiratorio/metabolismo , Proteínas Supresoras de Tumor/genética , Animales , Autoantígenos/genética , Autoantígenos/metabolismo , Dineínas Axonemales/genética , Dineínas Axonemales/metabolismo , Biomarcadores/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cilios/metabolismo , Cilios/patología , Proteínas del Citoesqueleto , Exoma , Regulación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Síndrome de Kartagener/metabolismo , Síndrome de Kartagener/patología , Masculino , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Mutación , Linaje , Unión Proteica , Estructura Terciaria de Proteína , Proteínas/metabolismo , Ratas , Sistema Respiratorio/patología , Proteínas Supresoras de Tumor/metabolismo , Xenopus laevis/genética , Xenopus laevis/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
Patients with circumcaval ureter and right renal calculi are not often seen in the clinical practice and require special approach. Hereby we report a case of a 34-year-old male that was diagnosed with circumcaval ureter complicated by right kidney stones. Laparoscopic ureteroplasty and flexible ureteroscopic lithotripsy were implemented in the treatment of both of these entities. A combination of these approaches allowed us to perform the surgery effectively, efficiently and safely without having to do the second one.