KIAA0586 is Mutated in Joubert Syndrome.

TitleKIAA0586 is Mutated in Joubert Syndrome.
Publication TypeJournal Article
Year of Publication2015
AuthorsBachmann-Gagescu, R, Phelps, IG, Dempsey, JC, Sharma, VA, Ishak, GE, Boyle, EA, Wilson, M, Lourenço, CMarques, Arslan, M, Shendure, J, Doherty, D
Corporate AuthorsUniversity of Washington Center for Mendelian Genomics
JournalHum Mutat
Date Published2015 Sep
KeywordsAbnormalities, Multiple, Adolescent, Adult, Alternative Splicing, Brain, Cell Cycle Proteins, Cerebellum, Child, Child, Preschool, DNA Mutational Analysis, Eye Abnormalities, Gene Order, Genetic Association Studies, Humans, Kidney Diseases, Cystic, Magnetic Resonance Imaging, Mutation, Phenotype, Retina, Young Adult

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.

Alternate JournalHum. Mutat.
PubMed ID26096313
PubMed Central IDPMC4537327
Grant ListU54 HG006493 / HG / NHGRI NIH HHS / United States
U54 HD083091 / HD / NICHD NIH HHS / United States
RC2 HG005608 / HG / NHGRI NIH HHS / United States
U54HD083091 / HD / NICHD NIH HHS / United States
U54HG006493 / HG / NHGRI NIH HHS / United States
R01NS064077 / NS / NINDS NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States
R01 NS064077 / NS / NINDS NIH HHS / United States