NPHP1 mutation caused different phenotypes in sibling: Joubert syndrome in brother and autism spectrum disorder in sister

Abstract

  Joubert syndrome is a congenital disorder caused by abnormalities in the primary cilia involving multiple organs such as brain and kidney. The disorder is caused by different genes including NPHP1. We experienced the brother with Joubert syndrome complicated with renal insufficiency. The sister of the patient, who was diagnosed with autism spectrum disorder, developed renal insufficiency. We identified a novel nonsense mutation in NPHP1gene (c.1639C>T; p.Q547*) which was possibly homozygous in siblings. Thus, the same NPHP1 mutation caused a phenotype compatible with Joubert syndrome as well as non-Joubert type disorders such as renal insufficiency and autism spectrum disorder. More patients will be needed for understanding the pathophysiology of Joubert syndrome.