title: Recessive mutations in the gene encoding the tight junction protein occludin cause band-like calcification with simplified gyration and polymicrogyria.
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.
authors: University of Manchester, Manchester Academic Health Science Centre, Central Manchester Foundation Trust University Hospitals, UK.
authors: Mary C
authors: MC
authors: O'Driscoll
authors: Sarah B
authors: SB
authors: Daly
authors: Jill E
authors: JE
authors: Urquhart
authors: Graeme C M
authors: GC
authors: Black
authors: Daniela T
authors: DT
authors: Pilz
authors: Knut
authors: K
authors: Brockmann
authors: Meriel
authors: M
authors: McEntagart
authors: Ghada
authors: G
authors: Abdel-Salam
authors: Maha
authors: M
authors: Zaki
authors: Nicole I
authors: NI
authors: Wolf
authors: Roger L
authors: RL
authors: Ladda
authors: Susan
authors: S
authors: Sell
authors: Stefano
authors: S
authors: D'Arrigo
authors: Waney
authors: W
authors: Squier
authors: William B
authors: WB
authors: Dobyns
authors: John H
authors: JH
authors: Livingston
authors: Yanick J
authors: YJ
authors: Crow
mesh_terms: D000818:Animals; D001483:Base Sequence; D002114:Calcinosis / Q000134:cerebrospinal fluid / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D006720:Homozygote; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D054220:Malformations of Cortical Development / Q000134:cerebrospinal fluid / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D062793:Occludin; D012984:Software; D019108:Tight Junctions / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse