RESUMEN
Alport syndrome (ATS) is a genetically heterogeneous nephropathy with considerable phenotypic variability and different transmission patterns, including monogenic (X-linked/autosomal) and digenic inheritance (DI). Here we present a new series of families with DI and we discuss the consequences for genetic counseling and risk assessment. Out of five families harboring variants in more than one COL4 gene detected by next generation sequencing (NGS), minigene-splicing assay allowed us to identify four as true digenic. Two families showed COL4A3/A4 mutations in cis, mimicking an autosomal dominant inheritance with a more severe phenotype and one showed COL4A3/A4 mutations in trans, mimicking an autosomal recessive inheritance with a less severe phenotype. In a fourth family, a de novo mutation (COL4A5) combined with an inherited mutation (COL4A3) triggered a more severe phenotype. A fifth family, predicted digenic on the basis of silico tools, rather showed monogenic X-linked inheritance due to a hypomorphic mutation, in accordance with a milder phenotype. In conclusion, this study highlights the impact of DI in ATS and explains the associated atypical presentations. More complex inheritance should be therefore considered when reviewing prognosis and recurrence risks. On the other side, these findings emphasize the importance to accompany NGS with splicing assays in order to avoid erroneous identification of at risk members.
Asunto(s)
Autoantígenos/genética , Colágeno Tipo IV/genética , Herencia Multifactorial/genética , Nefritis Hereditaria/genética , Adulto , Anciano , Femenino , Genes Ligados a X , Asesoramiento Genético , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Nefritis Hereditaria/fisiopatología , Linaje , Medición de RiesgoRESUMEN
The emphysematous cystitis is a rare condition, usually with a favorable prognosis; it is characterized by the presence of air in the bladder lumen and/or wall caused by the fermentation of glucose due to the action of microorganisms. Here the case is described of a hemodialyzed diabetic oligoanuric patient suffering from frequent symptomatic relapses of urinary tract infection, with air in the bladder and reported pneumaturia. The diagnostic workup aimed to exclude the presence of enterovesical fistulas, which are a possible cause of the presence of air in the urinary tract. The air was produced by bacteria isolated in the urine culture. Both the dysuric symptoms and the gas disappeared after appropriate antibiotic treatment.