Journal article
Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly
American journal of human genetics, Vol.99(5), pp.1181-1189
11/03/2016
DOI: 10.1016/j.ajhg.2016.09.007
PMCID: PMC5097947
PMID: 27773428
Abstract
Cobblestone lissencephaly (COB) is a severe brain malformation in which overmigration of neurons and glial cells into the arachnoid space results in the formation of cortical dysplasia. COB occurs in a wide range of genetic disorders known as dystroglycanopathies, which are congenital muscular dystrophies associated with brain and eye anomalies and range from Walker-Warburg syndrome to Fukuyama congenital muscular dystrophy. Each of these conditions has been associated with alpha-dystroglycan defects or with mutations in genes encoding basement membrane components, which are known to interact with alpha-dystroglycan. Our screening of a cohort of 25 families with recessive forms of COB identified six families affected by biallelic mutations in TMTC3 (encoding transmembrane and tetratricopeptide repeat containing 3), a gene without obvious functional connections to alpha-dystroglycan. Most affected individuals showed brainstem and cerebellum hypoplasia, as well as ventriculomegaly. However, the minority of the affected individuals had eye defects or elevated muscle creatine phosphokinase, separating the TMTC3 COB phenotype from typical congenital muscular dystrophies. Our data suggest that loss of TMTC3 causes COB with minimal eye or muscle involvement.
Details
- Title: Subtitle
- Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly
- Creators
- Julie Jerber - Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USAMaha S Zaki - Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo 12311, EgyptJumana Y Al-Aama - Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21453, Saudi ArabiaRasim Ozgur Rosti - Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USATawfeg Ben-Omran - Clinical and Metabolic Genetics Section, Department of Pediatrics, Hamad Medical Corporation, PO Box 3050, Doha, QatarEsra Dikoglu - Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USAJennifer L Silhavy - Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USACaner Caglar - Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USADamir Musaev - Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USABeate Albrecht - Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, 45122 Essen, GermanyKevin P Campbell - Howard Hughes Medical Institute, Departments of Neurology, Internal Medicine, and Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1101, USATobias Willer - Howard Hughes Medical Institute, Departments of Neurology, Internal Medicine, and Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1101, USAMariam Almuriekhi - Clinical and Metabolic Genetics Section, Department of Pediatrics, Hamad Medical Corporation, PO Box 3050, Doha, QatarAhmet Okay Çağlayan - Department of Medical Genetics, School of Medicine, Istanbul Bilim University, Istanbul 34394, TurkeyJiri Vajsar - Division of Neurology, The Hospital for Sick Children, Toronto, ON M5G 1X8, CanadaKaya Bilgüvar - Yale Program on Neurogenetics, Departments of Neurosurgery, Neurobiology, and Genetics, School of Medicine, Yale University, New Haven, CT 06510, USAGonul Ogur - Department of Genetics, School of Medicine, Ondokuz Mayis University, 55000 Samsun, TurkeyRami Abou Jamra - Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Philipp-Rosenthal-Str. 55, 04103 Leipzig, GermanyMurat Günel - Yale Program on Neurogenetics, Departments of Neurosurgery, Neurobiology, and Genetics, School of Medicine, Yale University, New Haven, CT 06510, USAJoseph G Gleeson - Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, NY 10065, USA
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.99(5), pp.1181-1189
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.ajhg.2016.09.007
- PMID
- 27773428
- PMCID
- PMC5097947
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Language
- English
- Date published
- 11/03/2016
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020501502771
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