NPHP3 mutations are associated with neonatal onset multiorgan polycystic disease in two siblings

Two siblings with a severe multiorgan polycystic disease presenting in the neonatal period were identified. their genetic testing identified compound heterozygous nphp3 gene mutations, parents being heterozygous carriers. the mutations included a splice-site (c.958-2a>g) and a missense mutation (c.2342g>a; p.g781d), both being extremely rare. nphp3 encodes for nephrocystin 3 present on the cilia-centrosome complex. we hypothesize that these mutations lead to defective cilia-based signaling, required for normal development of the renal, pancreatic, biliary and portal system. this report outlines a rare neonatal ciliopathy presentation of nphp3 mutations leading to severe multiorgan failure in two siblings.