RESUMEN
Screening for disease-causing mutations in the unique region of the polycystic kidney disease 1 (PKD1) gene was performed in 41 unrelated individuals with autosomal dominant polycystic kidney disease. Exons 34-41 and 43-46 were assayed using PCR amplification and SSCP analysis followed by direct sequencing of amplicons presenting variant SSCP patterns. We have identified seven disease-causing mutations of which five are novel [c.10634-10656del; c.11587delG; IVS37-10C>A; c.11669-11674del; c.13069-13070ins39] and two have been reported previously [Q4010X; Q4041X]. Defects in this part of the gene thus account for 17% of our group of patients. Five of the seven sequence alterations detected are protein-truncating which is in agreement with mutation screening data for this part of the gene by other groups. The two other mutations are in-frame deletions or insertions which could destroy important functional properties of polycystin 1. These findings suggest that the first step toward cyst formation in PKD1 patients is the loss of one functional copy of polycystin 1, which indirectly supports the "two-hit" model of cystogenesis where a second somatic mutation inactivating the normal allele is necessary to occur for development of the disease condition.
Asunto(s)
Regiones no Traducidas 3'/genética , Mutación/genética , Riñón Poliquístico Autosómico Dominante/genética , Proteínas/genética , Adulto , Anciano , Empalme Alternativo/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos/genética , Australia/epidemiología , Bulgaria/epidemiología , Codón de Terminación/genética , Femenino , Pruebas Genéticas , Glutamina/genética , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutagénesis Insercional , Mutación Puntual/genética , Riñón Poliquístico Autosómico Dominante/epidemiología , Prevalencia , Canales Catiónicos TRPPRESUMEN
The authors wish to correct a mistake which occurred in the reporting of one of the mutations. The mutation in Cx32 Met34Lys is wrongly described as 100A>G. The correct description of the mutation should be 101T>A (Met34Lys).