title: LIS1 duplication: expanding the phenotype.
abstract: Disruptions to LIS1 gene expression result in neuronal migration abnormalities. LIS1 heterozygosity is a significant cause of lissencephaly, while overexpression has recently been noted in cases of microcephaly, ventriculomegaly, and dysgenesis of the corpus callosum with normal cortical gyration. We report a partial LIS1 duplication in a child with microcephaly, neurodevelopmental delays, and profound white matter atrophy in the absence of overt lissencephaly. The duplicated genetic segment was contained entirely within the first intron of LIS1, a segment that often contains inducers of transcription. Normal gyral patterns with mild volume loss were observed at birth. Follow-up cranial imaging revealed further white matter loss, diminished sulcation, and ventriculomegaly, suggesting expanding hydrocephalus ex vacuo. The radiographic pattern has not been documented in the presence of a LIS1 gene abnormality, and suggests that altered expression of LIS1 has wider phenotypic manifestations than currently defined.
authors.affiliation: Department of Neurosciences (Neurology), Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lockrow
authors.forename: Kenton R
authors.initials: KR
authors.lastname: Holden
authors.forename: Alka
authors.initials: A
authors.lastname: Dwivedi
authors.forename: Maria G
authors.initials: MG
authors.lastname: Matheus
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D005500:Follow-Up Studies; D020131:Genes, Duplicate / Q000235:genetics*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D046228:Microarray Analysis; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D010641:Phenotype; D011859:Radiography; D015898:Tomography Scanners, X-Ray Computed
chemical_list: D008869:Microtubule-Associated Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human