Formation of the B9-domain protein complex MKS1–B9D2–B9D1 is essential as a diffusion barrier for ciliary membrane proteins

Meckel syndrome (MKS)1, B9 domain (B9D)1, and B9D2 are soluble transition zone (TZ) proteins and share a B9D. We demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and their interdependent localization to the TZ. We also show that formation of the B9D protein complex is crucial for creating a diffusion barrier for ciliary membrane proteins.

Renal–Hepatic–Pancreatic Dysplasia: An Ultra-Rare Ciliopathy with a Novel NPHP3 Genotype

Renal–hepatic–pancreatic dysplasia-1 (RHPD1) is an ultra-rare genetic disorder with a high mortality. It is caused by biallelic pathogenic variants in NPHP3, which encode nephrocytin, an important component of the ciliary protein complex. The NPHP3-related disease phenotype is diverse with RHPD1, nephronophthisis-3, and Meckel syndrome-7. In this case report, we present a female infant with hepatomegaly, cholestasis, and elevated transaminases who was found to carry a homozygous c.2975C > T variant of NPHP3. This is the first description of this genotype and RHPD1 phenotype in the literature. The patient is currently being closely monitored for the necessity of combined renal and liver transplantation under supportive treatment.