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Am J Med Genet A. 2019 Dec;179(12):2343-2356. doi: 10.1002/ajmg.a.61342. Epub 2019 Oct 29.

Duplication 2p16 is associated with perisylvian polymicrogyria.

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Neurogenetics Unit, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada.
Department of Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada.
Department of Neurology, Hôpital Universitaire des Enfants Reine Fabiola (HUDERF), Université Libre de Bruxelles (ULB), Brussels, Belgium.
Division of Epilepsy & Clinical Neurophysiology, Children's Hospital, Boston, Massachusetts.
Department of Neurology, Children's Hospital, Boston, Massachusetts.
Ludmer Centre for Neuroinformatics and Mental Health and the Department of Biomedical Engineering, McGill Centre for Integrative Neuroscience, McGill University, Montreal, Quebec, Canada.
Department of Medical Genetics, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Genome Quebec Innovation Center, McGill University, Montreal, Quebec, Canada.
Epilepsy Research Group, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada.
Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
Division of Genetics and Manton Center for Orphan Disease Research, Children's Hospital, Boston, Massachusetts.
Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts.
Department of Pediatrics (Genetics) and Neurology, University of Washington, and Seattle Children's Research Institute, Seattle, Washington.


Polymicrogyria (PMG) is a heterogeneous brain malformation that may result from prenatal vascular disruption or infection, or from numerous genetic causes that still remain difficult to identify. We identified three unrelated patients with polymicrogyria and duplications of chromosome 2p, defined the smallest region of overlap, and performed gene pathway analysis using Cytoscape. The smallest region of overlap in all three children involved 2p16.1-p16.3. All three children have bilateral perisylvian polymicrogyria (BPP), intrauterine and postnatal growth deficiency, similar dysmorphic features, and poor feeding. Two of the three children had documented intellectual disability. Gene pathway analysis suggested a number of developmentally relevant genes and gene clusters that were over-represented in the critical region. We narrowed a rare locus for polymicrogyria to a region of 2p16.1-p16.3 that contains 33-34 genes, 23 of which are expressed in cerebral cortex during human fetal development. Using pathway analysis, we showed that several of the duplicated genes contribute to neurodevelopmental pathways including morphogen, cytokine, hormonal and growth factor signaling, regulation of cell cycle progression, cell morphogenesis, axonal guidance, and neuronal migration. These findings strengthen the evidence for a novel locus associated with polymicrogyria on 2p16.1-p16.3, and comprise the first step in defining the underlying genetic etiology.


chromosome 2; duplication 2p16.1-p16.3; growth retardation; intellectual disability; polymicrogyria


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