Cited by 26Genomic variations and chromosomal abnormalitiesFetal and Pediatric Neurological DisordersGenetics and Neurodevelopmental Disorders

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

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Shiba, Naoko, Daza, Ray AM, Shaffer, Lisa G, Barkovich, A James, Dobyns, William B, Hevner, Robert F·2013·Acta Neuropathologica Communications

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.

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  • In all human chromosomal aberration syndromes, including trisomies, monosomies, polyploidies, disomies and imprinting errors or sex chromosome anomalies, structural abnormalities of (pre)frontal as well as many other areas are common.

    “In all human chromosomal aberration syndromes, including trisomies, monosomies (e.g., Turner syndrome, monosomy 1p36), polyploidies, disomies and imprinting errors or sex chromosome anomalies, structural abnormalities of (pre)frontal as well as many other areas are common [61, 288–292].”

    From Development of prefrontal cortex (2022) · cites this paper as [61]

    The Results describe frontal cortical dysgenesis and abnormalities in several other regions in a patient with monosomy 1p36, supporting this syndrome as an example. The Background says significant developmental brain malformations occur in only some cases, and this single-case study does not establish that frontal abnormalities are common in monosomy 1p36. It does not address the other chromosomal syndromes in the citing sentence. (LLM, conf=0.84)

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Authors
Shiba, N., Daza, R. A., Shaffer, L. G., Barkovich, A. J., Dobyns, W. B., & Hevner, R. F.
Affiliations
  • Seattle Children's Research Institute (US)
  • University of California, San Francisco (US)
  • University of Washington (US)
Corresponding author
Hevner, Robert F
Venue
Acta Neuropathologica Communications
Published
2013-08-02
Volume
1
Issue
1
Pages
45-45
ISSN
2051-5960 (ISSN-L)
OpenAlex
W2144301600
Cited by
26
References
76
Citations by year
2022: 1 · 2021: 2 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 1
FWCI
1.55
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
subtelomeric deletion, brain malformations, spinal malformations, polymicrogyria, nodular heterotopia, cortical dysgenesis, microcephaly, hippocampal malrotation, cerebellar vermis, Hes genes, p73, neurodevelopmental genes, intellectual disability, seizures
MeSH terms
Abnormalities, Multiple, Brain, Child, Chromosome Deletion, Chromosomes, Human, Pair 1, Female, Humans, Infant, Magnetic Resonance Imaging, Spinal Cord, Fatal Outcome

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