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

KIAA0586 is Mutated in Joubert Syndrome.

Author information

1
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
2
Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.
3
Department of Pediatrics, University of Washington, Seattle, Washington.
4
Department of Radiology, Seattle Children's Hospital, University of Washington, Seattle, Washington.
5
Department of Genome Sciences, University of Washington, Seattle, Washington.
6
Department of Genetics, Stanford University, Stanford, Washington.
7
Department of Clinical Genetics, Children's Hospital at Westmead, Sydney, NSW, Australia.
8
Department of Neurosciences and Behavior Neurosciences, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
9
Gulhane Military Medical School, Division of Child Neurology, Ankara, Turkey.

Abstract

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

PMID:
26096313
PMCID:
PMC4537327
DOI:
10.1002/humu.22821
[Indexed for MEDLINE]
Free PMC Article

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