RESUMEN
BACKGROUND: Dandy-Walker malformation features agenesis/hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle and enlargement of posterior fossa. Although Dandy-Walker malformation is relatively common and several genes were linked to the syndrome, the genetic cause in the majority of cases is unknown. OBJECTIVE: To identify the mutated gene responsible for Dandy-Walker malformation, kidney disease and bone marrow failure in four patients from two unrelated families. METHODS: Medical assessment, sonographic, MRI and pathological studies were used to define phenotype. Chromosomal microarray analysis and whole-exome sequence were performed to unravel the genotype. RESULTS: We report four subjects from two unrelated families with homozygous mutations in the Exocyst Complex Component 3-Like-2 gene (EXOC3L2).EXOC3L2 functions in trafficking of post-Golgi vesicles to the plasma membrane. In the first family a missense mutation in a highly conserved amino acid, p.Leu41Gln, was found in three fetuses; all had severe forms of Dandy-Walker malformation that was detectable by prenatal ultrasonography and confirmed by autopsy. In the second family, the affected child carried a nonsense mutation, p.Arg72*, and no detected protein. He had peritrigonal and cerebellar white matter abnormalities with enlargement of the ventricular trigones, developmental delay, pituitary hypoplasia, severe renal dysplasia and bone marrow failure. CONCLUSION: We propose that biallelic EXOC3L2 mutations lead to a novel syndrome that affects hindbrain development, kidney and possibly the bone marrow.
Asunto(s)
Alelos , Síndrome de Dandy-Walker/diagnóstico , Síndrome de Dandy-Walker/genética , Mutación , Fenotipo , Proteínas de Transporte Vesicular/genética , Biopsia , Encéfalo/patología , Variaciones en el Número de Copia de ADN , Homocigoto , Humanos , Riñón/metabolismo , Imagen por Resonancia Magnética , Evaluación de Síntomas , Síndrome , Ultrasonografía , Proteínas de Transporte Vesicular/metabolismo , Secuenciación del ExomaRESUMEN
Schwannomas of the nasal cavity are extremely rare. We evaluated a 42-year-old woman who presented with a 4-year history of slowly progressive nasal obstruction. The cause of the obstruction was identified as a schwannoma in the left inferior turbinate. The tumor was completely excised, and no sign of recurrence was evident at the 1-year follow-up. To the best of our knowledge, this is only the third case of a schwannoma originating in the inferior nasal turbinate that has been reported in the English-language literature. We review the clinical and pathologic features of this case.