Skip to main content
eScholarship
Open Access Publications from the University of California

Neuropathology of brain and spinal malformations in a case of monosomy 1p36

  • Author(s): Shiba, Naoko
  • Daza, Ray AM
  • Shaffer, Lisa G
  • Barkovich, A
  • Dobyns, William B
  • Hevner, Robert F
  • et al.
Abstract

Abstract Monosomy 1p36 is the most common subtelomeric chromosomal deletion linked to mental retardation and seizures. Neuroimaging studies suggest that monosomy 1p36 is associated with brain malformations including polymicrogyria and nodular heterotopia, but the histopathology of these lesions is unknown. Here we present postmortem neuropathological findings from a 10 year-old girl with monosomy 1p36, who died of respiratory complications. The findings included micrencephaly, periventricular nodular heterotopia in occipitotemporal lobes, cortical dysgenesis resembling polymicrogyria in dorsolateral frontal lobes, hippocampal malrotation, callosal hypoplasia, superiorly rotated cerebellum with small vermis, and lumbosacral hydromyelia. The abnormal cortex exhibited “festooned” (undulating) supragranular layers, but no significant fusion of the molecular layer. Deletion mapping demonstrated single copy loss of a contiguous 1p36 terminal region encompassing many important neurodevelopmental genes, among them four HES genes implicated in regulating neural stem cell differentiation, and TP73, a monoallelically expressed gene. Our results suggest that brain and spinal malformations in monosomy 1p36 may be more extensive than previously recognized, and may depend on the parental origin of deleted genes. More broadly, our results suggest that specific genetic disorders may cause distinct forms of cortical dysgenesis.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Main Content
Current View