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KIAA0586 is Mutated in Joubert Syndrome.
Hum Mutat. 2015 Sep; 36(9):831-5.HM

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.

Authors+Show Affiliations

Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland. Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.Department of Pediatrics, University of Washington, Seattle, Washington.Department of Pediatrics, University of Washington, Seattle, Washington.Department of Pediatrics, University of Washington, Seattle, Washington.Department of Radiology, Seattle Children's Hospital, University of Washington, Seattle, Washington.Department of Genome Sciences, University of Washington, Seattle, Washington. Department of Genetics, Stanford University, Stanford, Washington.Department of Clinical Genetics, Children's Hospital at Westmead, Sydney, NSW, Australia.Department of Neurosciences and Behavior Neurosciences, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.Gulhane Military Medical School, Division of Child Neurology, Ankara, Turkey.No affiliation info availableDepartment of Genome Sciences, University of Washington, Seattle, Washington.Department of Pediatrics, University of Washington, Seattle, Washington.

Pub Type(s)

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

Language

eng

PubMed ID

26096313

Citation

Bachmann-Gagescu, Ruxandra, et al. "KIAA0586 Is Mutated in Joubert Syndrome." Human Mutation, vol. 36, no. 9, 2015, pp. 831-5.
Bachmann-Gagescu R, Phelps IG, Dempsey JC, et al. KIAA0586 is Mutated in Joubert Syndrome. Hum Mutat. 2015;36(9):831-5.
Bachmann-Gagescu, R., Phelps, I. G., Dempsey, J. C., Sharma, V. A., Ishak, G. E., Boyle, E. A., Wilson, M., Marques Lourenço, C., Arslan, M., Shendure, J., & Doherty, D. (2015). KIAA0586 is Mutated in Joubert Syndrome. Human Mutation, 36(9), 831-5. https://doi.org/10.1002/humu.22821
Bachmann-Gagescu R, et al. KIAA0586 Is Mutated in Joubert Syndrome. Hum Mutat. 2015;36(9):831-5. PubMed PMID: 26096313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - KIAA0586 is Mutated in Joubert Syndrome. AU - Bachmann-Gagescu,Ruxandra, AU - Phelps,Ian G, AU - Dempsey,Jennifer C, AU - Sharma,Vivek A, AU - Ishak,Gisele E, AU - Boyle,Evan A, AU - Wilson,Meredith, AU - Marques Lourenço,Charles, AU - Arslan,Mutluay, AU - ,, AU - Shendure,Jay, AU - Doherty,Dan, Y1 - 2015/07/02/ PY - 2015/04/27/received PY - 2015/06/08/accepted PY - 2015/6/23/entrez PY - 2015/6/23/pubmed PY - 2016/5/11/medline KW - Joubert syndrome KW - KIAA0586 KW - Talpid3 KW - ciliopathy KW - sonic hedgehog SP - 831 EP - 5 JF - Human mutation JO - Hum. Mutat. VL - 36 IS - 9 N2 - 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. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/26096313/KIAA0586_is_Mutated_in_Joubert_Syndrome_ L2 - https://doi.org/10.1002/humu.22821 DB - PRIME DP - Unbound Medicine ER -