Duplication 2p16 is associated with perisylvian polymicrogyria

Dina Amrom, Annapurna Poduri, Jennifer S Goldman, Bernard Dan, Nicolas Deconinck, Bruno Pichon, Javad Nadaf, Frederick Andermann, Eva Andermann, Christopher A Walsh, William B Dobyns

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Pages (from-to)2343-2356
Number of pages14
JournalAmerican Journal of Medical Genetics. Part A
Issue number12
Publication statusPublished - Dec 2019

Bibliographical note

© 2019 Wiley Periodicals, Inc.


  • Abnormalities, Multiple/diagnosis
  • Adolescent
  • Brain/abnormalities
  • Chromosome Duplication
  • Chromosomes, Human, Pair 2
  • Comparative Genomic Hybridization
  • Computational Biology/methods
  • Facies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Infant, Newborn
  • Intellectual Disability/diagnosis
  • Magnetic Resonance Imaging
  • Male
  • Malformations of Cortical Development/diagnosis
  • Phenotype


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