Mutations PKHD1 dans la polykystose autosomique récessive : corrélations génotype–phénotype dans une série de 308 cas pour guider le diagnostic anténatal

Abstract

ObjectivesARPKD is a recessive rare disease due to PKHD1 mutation. The main objective of the study was to characterize the phenotypic variability according to the different types of PKHD1 mutations. MethodsThis study was performed in 308 ARPKD patients with a genetic diagnosis from our genetic center. Related physicians provided minimal clinical and biological data. ResultsPatients were divided into three genotypic groups: the first group (G1; n=65) consisted of patients with two truncating mutations, the second group (G2; n=117) of patients with one truncating and one non-truncating mutation, and the third group (G3; n=126) of patients with two non-truncating mutations. In the entire cohort, the outcomes consisted of 31% of pregnancy termination, 18% of neonatal deaths and 51% of patient survival after the neonatal period. The proportion of severe ARPKD (pregnancy termination or neonatal death) was significantly greater in G1: 94% versus 47% in G2 and 27% in G3 (P<0.001). ConclusionThe presence of two truncating mutations in PKHD1 is associated with the most severe perinatal phenotype. However, the phenotypic variability observed in the other genotypic groups requires caution for prenatal counseling.