TMEM218 dysfunction causes ciliopathies, including Joubert and Meckel syndromes.


Journal

HGG advances
ISSN: 2666-2477
Titre abrégé: HGG Adv
Pays: United States
ID NLM: 101772885

Informations de publication

Date de publication:
14 Jan 2021
Historique:
entrez: 1 4 2021
pubmed: 2 4 2021
medline: 2 4 2021
Statut: ppublish

Résumé

The Joubert-Meckel syndrome spectrum is a continuum of recessive ciliopathy conditions caused by primary cilium dysfunction. The primary cilium is a microtubule-based, antenna-like organelle that projects from the surface of most human cell types, allowing them to respond to extracellular signals. The cilium is partitioned from the cell body by the transition zone, a known hotspot for ciliopathy-related proteins. Despite years of Joubert syndrome (JBTS) gene discovery, the genetic cause cannot be identified in up to 30% of individuals with JBTS, depending on the cohort, sequencing method, and criteria for pathogenic variants. Using exome and targeted sequencing of 655 families with JBTS, we identified three individuals from two families harboring biallelic, rare, predicted-deleterious missense

Identifiants

pubmed: 33791682
doi: 10.1016/j.xhgg.2020.100016
pmc: PMC8009330
mid: NIHMS1663070
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : NICHD NIH HHS
ID : P50 HD103524
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD100730
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD083091
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006493
Pays : United States

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Julie C Van De Weghe (JC)

Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.

Jessica L Giordano (JL)

Department of OB/GYN, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

Inge B Mathijssen (IB)

Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Majid Mojarrad (M)

Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Genetic Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Genetic Center of Khorasan Razavi, Mashhad, Iran.

Dorien Lugtenberg (D)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.

Caitlin V Miller (CV)

Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.

Jennifer C Dempsey (JC)

Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.

Mahsa Sadat Asl Mohajeri (MSA)

Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Elizabeth van Leeuwen (E)

Department of Obstetrics and Gynecology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Eva Pajkrt (E)

Department of Obstetrics and Gynecology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Caroline C W Klaver (CCW)

Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.

Henry Houlden (H)

Department of Neuromuscular Disorders, University College London Institute of Neurology, Queen Square, London WC1N 3BG, UK.

Atieh Eslahi (A)

Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Aoife M Waters (AM)

Great Ormond Street Hospital NHS Foundation Trust, London WC1N 1LE, UK.

Michael J Bamshad (MJ)

Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
University of Washington Center for Mendelian Genomics, Seattle, WA 98195, USA.
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.

Deborah A Nickerson (DA)

University of Washington Center for Mendelian Genomics, Seattle, WA 98195, USA.
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.

Vimla S Aggarwal (VS)

Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032 USA.

Bert B A de Vries (BBA)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.

Reza Maroofian (R)

Department of Neuromuscular Disorders, University College London Institute of Neurology, Queen Square, London WC1N 3BG, UK.

Dan Doherty (D)

Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101 USA.
Twitter: @Dohertylab.

Classifications MeSH