Recessive mutations in the gene encoding the tight junction protein occludin cause band-like calcification with simplified gyration and polymicrogyria

Mary C O'Driscoll, Sarah B Daly, Jill E Urquhart, Graeme C M Black, Daniela T Pilz, Knut Brockmann, Meriel McEntagart, Ghada Abdel-Salam, Maha Zaki, Nicole I Wolf, Roger L Ladda, Susan Sell, Stefano D'Arrigo, Waney Squier, William B Dobyns, John H Livingston, Yanick J Crow

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)354-64
Number of pages11
JournalAmerican Journal of Human Genetics
Issue number3
Publication statusPublished - 10 Sep 2010


  • Animals
  • Base Sequence
  • Calcinosis
  • Cerebral Cortex
  • Chromosomes, Human, Pair 5
  • Consanguinity
  • DNA Mutational Analysis
  • Gene Expression Regulation
  • Homozygote
  • Humans
  • In Situ Hybridization
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Malformations of Cortical Development
  • Membrane Proteins
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Occludin
  • Software
  • Tight Junctions
  • Journal Article
  • Research Support, Non-U.S. Gov't


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