|
|||||
|
|
Recessive Mutations in the Gene Encoding the Tight Junction Protein Occludin Cause Band-like Calcification with Simplified Gyration and Polymicrogyria |
|
| Authors: | Mary C. O'Driscoll Jill E. Urquhart Daniela T. Pilz Meriel McEntagart Maha Zaki Roger L. Ladda Stefano D'Arrigo William B. Dobyns Yanick J. Crow |
| Affiliation: | 1 Genetic Medicine, University of Manchester, Manchester Academic Health Science Centre, Central Manchester Foundation Trust University Hospitals, Manchester, M13 9WL, UK 2 Department of Medical Genetics, University Hospital of Wales, Cardiff, CF14 4XW, UK 3 Department of Paediatrics and Paediatric Neurology, Children's Hospital, Georg August University, Robert-Koch-Str. 40, 37075, Goettingen, Germany 4 Department of Clinical Genetics, St. George's Hospital, London, SW17 0RE, UK 5 Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, 12311, Egypt 6 Paediatric Neurology, University Children's Hospital, 69120 Heidelberg, Germany 7 Department of Child Neurology, VU Medical Center, 1007 MB Amsterdam, The Netherlands 8 Division of Human Genetics, Growth & Development, Department of Pediatrics, Penn State Hershey Children's Hospital, Hershey, PA 17033, USA 9 Development Neurology Department, Fondazione IRCCS Istituto Neurologico “C. Besta,” 20133 Milan, Italy 10 Departments of Neurology and Neuropathology, Radcliffe Infirmary, Oxford, OX3 9DU, UK 11 Departments of Human Genetics, Neurology and Pediatrics, The University of Chicago, Chicago, IL 60637, USA 12 Department of Paediatric Neurology, Leeds General Infirmary, Leeds, LS9 7TF, UK |
| Abstract: | Band-like calcification with simplified gyration and polymicrogyria (BLC-PMG) is a rare autosomal-recessive neurological disorder showing highly characteristic clinical and neuroradiological features. Affected individuals demonstrate early-onset seizures, severe microcephaly, and developmental arrest with bilateral, symmetrical polymicrogyria (PMG) and a band of gray matter calcification on brain imaging; as such, the disorder can be considered as a “pseudo-TORCH” syndrome. By using autozygosity mapping and copy number analysis we identified intragenic deletions and mutations in OCLN in nine patients from six families with BLC-PMG. The OCLN gene encodes occludin, an integral component of tight junctions. Neuropathological analysis of an affected individual showed similarity to the mouse model of occludin deficiency with calcification predominantly associated with blood vessels. Both intracranial calcification and PMG are heterogeneous in etiology. Neuropathological and clinical studies of PMG have suggested that in utero ischemic or vascular insults may contribute to this common cortical abnormality. Tight junctions are functional in cerebral blood vessels early in fetal development and continue to play a vital role in maintenance of the blood-brain barrier during postnatal life. We provide evidence that the tight junction protein occludin (encoded by the OCLN gene) is involved in the pathogenesis of malformations of cortical development. |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ | |