The proposed program project (PP) will examine the basis of neuronal migration in the forebrain. The focal point of the PP will be the study of the molecular basis of classical lissencephaly and subcortical band heterotopia, which are now recognized to constitute a spectrum of brain malformations whose fundamental morphologic phenotype reflects disordered migration of cortical neurons. Recent data, derived from the laboratories of the PP investigators, have defined two specific molecular defects as the basis for these distinct malformations (LIS1 on chromosome 17p13.3 and XLIS/DBCN on Xq22.3-q23). The clinical consequences can be very substantial -- intractable epilepsy and severe mental retardation. The proposed PP, which emanates from the close collaborative efforts of the PP investigators over the past 10-15 years, consists of four individual projects and three Cores. Projects 1 and 2 deal mainly with LIS1 and Projects 3 and 4 mainly with XLIS/DBCN. Cores A and B are developed to provide the clinical and diagnostic services for Projects 1,3, and 4. Core C will provide transgenic animals for Projects 2, 3, and 4.
| Brock, Stefanie; Stouffs, Katrien; Scalais, Emmanuel et al. (2018) Tubulinopathies continued: refining the phenotypic spectrum associated with variants in TUBG1. Eur J Hum Genet 26:1132-1142 |
| Di Donato, Nataliya; Timms, Andrew E; Aldinger, Kimberly A et al. (2018) Analysis of 17 genes detects mutations in 81% of 811 patients with lissencephaly. Genet Med 20:1354-1364 |
| Di Donato, Nataliya; Chiari, Sara; Mirzaa, Ghayda M et al. (2017) Lissencephaly: Expanded imaging and clinical classification. Am J Med Genet A 173:1473-1488 |
| Di Donato, Nataliya; Kuechler, Alma; Vergano, Samantha et al. (2016) Update on the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome. Am J Med Genet A 170:2644-51 |
| Parrini, Elena; Conti, Valerio; Dobyns, William B et al. (2016) Genetic Basis of Brain Malformations. Mol Syndromol 7:220-233 |
| Labelle-Dumais, Cassandre; Dilworth, David J; Harrington, Emily P et al. (2011) COL4A1 mutations cause ocular dysgenesis, neuronal localization defects, and myopathy in mice and Walker-Warburg syndrome in humans. PLoS Genet 7:e1002062 |
| Leventer, Richard J; Jansen, Anna; Pilz, Daniela T et al. (2010) Clinical and imaging heterogeneity of polymicrogyria: a study of 328 patients. Brain 133:1415-27 |
| Nicholas, Adeline K; Khurshid, Maryam; Désir, Julie et al. (2010) WDR62 is associated with the spindle pole and is mutated in human microcephaly. Nat Genet 42:1010-4 |
| Haverfield, Eden V; Whited, Amanda J; Petras, Kristin S et al. (2009) Intragenic deletions and duplications of the LIS1 and DCX genes: a major disease-causing mechanism in lissencephaly and subcortical band heterotopia. Eur J Hum Genet 17:911-8 |
| Dobyns, William B; Mirzaa, Ghayda; Christian, Susan L et al. (2008) Consistent chromosome abnormalities identify novel polymicrogyria loci in 1p36.3, 2p16.1-p23.1, 4q21.21-q22.1, 6q26-q27, and 21q2. Am J Med Genet A 146A:1637-54 |
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