New mutation associated with autosomal dominant polycystic kidney disease with founder effect located in the Alpujarra region of Granada

To demonstrate that the variant not described in PKD1 gene c.7292T> A, identified in four families from the Alpujarra in Granada, is the cause of autosomal dominant polycystic kidney disease (ADPKD). This variant consists of a transversion of thymine (T) by adenine (A) that at the level of the Polycystin 1 protein produces a change of leucine (Leu/L) by Glutamine (Gln/Q) in position 2431 (p.Leu2431Gln). Sociodemographic and clinical variables were registered using clinical histories, genealogical trees, ultrasounds and genetic analysis to ADPKD and healthy individuals belonging to these families in the context of segregation study. All PKD individuals carried the c.7292T> A variant in heterozygosis, whereas healthy ones did not. Among all ADPKD patients, 62.9% were women. ADPKD diagnosis was made at 29.3 ± 15.82 years, after having the first child in 64.8%. The main reasons for diagnosis were family history and hematuria episodes. The onset of renal replacement therapy (RRT) occurred at 55.8 ± 7.62 years (range 44–67), and death at 63 ± 92.2 years (range 48–76), being the cause unknown, cardiovascular and insufficiency kidney the most frequent; the median of renal survival was established at 58.5 ± 0.77 years and the median survival of patients at 67.2 ± 3.54 years. No differences in kidney and patient survivals were observed according to sex. Among deceased patients, 52.2% required RRT and 94.4% suffered from renal failure. The variant c.7292T> A in PKD1 gene is responsible for the disease, and its distribution in the Alpujarra region of Granada suggests a founder effect. In ADPKD it is necessary to perform segregation studies that help us to reclassify genetic variants, in this case from indeterminate to pathogenic. Demostrar que la variante no descrita en el gen PKD1 c.7292T> A, identificada en cuatro familias de la comarca de la Alpujarra de Granada, es la causante de poliquistosis renal autosómica dominante (PQRAD). Esta variante consiste en una sustitución transversión de timina (T) por adenina (A) que a nivel de la proteína Policistina 1 produce un cambio de leucina (Leu/L) por Glutamina (Gln/Q) en posición 2431 (p.Leu2431Gln). Registramos variables sociodemográficas y clínicas a través de la realización de historias clínicas, árboles genealógicos, ecografías y estudios genéticos a individuos afectos y sanos pertenecientes a estas familias en el contexto del estudio de segregación. Todos los individuos afectados portaban en heterocigosis la variante