KIAA0586 is Mutated in Joubert Syndrome

Hum Mutat. 2015 Sep;36(9):831-5. doi: 10.1002/humu.22821. Epub 2015 Jul 2.


Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by a distinctive mid-hindbrain malformation. JS is part of a group of disorders called ciliopathies based on their overlapping phenotypes and common underlying pathophysiology linked to primary cilium dysfunction. Biallelic mutations in one of 28 genes, all encoding proteins localizing to the primary cilium or basal body, can cause JS. Despite this large number of genes, the genetic cause can currently be determined in about 62% of individuals with JS. To identify novel JS genes, we performed whole exome sequencing on 35 individuals with JS and found biallelic rare deleterious variants (RDVs) in KIAA0586, encoding a centrosomal protein required for ciliogenesis, in one individual. Targeted next-generation sequencing in a large JS cohort identified biallelic RDVs in eight additional families for an estimated prevalence of 2.5% (9/366 JS families). All affected individuals displayed JS phenotypes toward the mild end of the spectrum.

Keywords: Joubert syndrome; KIAA0586; Talpid3; ciliopathy; sonic hedgehog.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics
  • Adolescent
  • Adult
  • Alternative Splicing
  • Brain / pathology
  • Cell Cycle Proteins / genetics*
  • Cerebellum / abnormalities*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Eye Abnormalities / diagnosis
  • Eye Abnormalities / genetics
  • Gene Order
  • Genetic Association Studies
  • Humans
  • Kidney Diseases, Cystic / diagnosis
  • Kidney Diseases, Cystic / genetics
  • Magnetic Resonance Imaging
  • Mutation*
  • Phenotype
  • Retina / abnormalities*
  • Young Adult


  • Cell Cycle Proteins
  • KIAA0586 protein, human

Supplementary concepts

  • Agenesis of Cerebellar Vermis