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Duplication 2p16 is associated with perisylvian polymicrogyria
Author(s) -
Amrom Dina,
Poduri Annapurna,
Goldman Jennifer S.,
Dan Bernard,
Deconinck Nicolas,
Pichon Bruno,
Nadaf Javad,
Andermann Frederick,
Andermann Eva,
Walsh Christopher A.,
Dobyns William B.
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61342
Subject(s) - polymicrogyria , gene duplication , locus (genetics) , biology , genetics , haploinsufficiency , gene , neuroscience , epilepsy , phenotype
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.