Please use this identifier to cite or link to this item: https://hdl.handle.net/11499/4351
Title: The role of RELN in lissencephaly and neuropsychiatric disease
Authors: Chang, B.S.
Düzcan, Füsun
Kim, S.
Cinbis, M.
Aggarwal, A.
Apse, K.A.
Özdel, Osman İsmail
Keywords: Cerebellar hypoplasia
Malformation of cortical development
Pachygyria
agyria
article
brain development
cerebellum hypoplasia
chromosome 7
clinical article
female
gene
gene locus
human
male
mental disease
paracentric chromosome inversion
pedigree
point mutation
preschool child
priority journal
reln gene
Brain
Cell Adhesion Molecules, Neuronal
Central Nervous System Diseases
Cerebellum
Cerebral Cortex
Child
Chromosomes, Human, Pair 7
Cytogenetics
Extracellular Matrix Proteins
Female
Heterozygote
Homozygote
Humans
In Situ Hybridization, Fluorescence
Inversion, Chromosome
Magnetic Resonance Imaging
Male
Mental Disorders
Nerve Tissue Proteins
Pedigree
Phenotype
Serine Endopeptidases
Abstract: Reelin is an extracellular matrix-associated protein important in the regulation of neuronal migration during cerebral cortical development. Point mutations in the RELN gene have been shown to cause an autosomal recessive human brain malformation termed lissencephaly with cerebellar hypoplasia (LCH). Recent work has raised the possibility that reelin may also play a pathogenic role in other neuropsychiatric disorders. We sought, therefore, to define more precisely the phenotype of RELN gene disruption. To do this, we performed a clinical, radiological, and molecular study of a family in whom multiple individuals carry a chromosomal inversion that disrupts the RELN locus. A 6-year-old girl homozygous for the pericentric inversion 46,XX,inv7(p11.2q22) demonstrated the same clinical features that have been previously described in association with RELN point mutations. The girl's brain magnetic resonance imaging (MRI) findings, including pachygyria and severe cerebellar hypoplasia, were identical to those seen with RELN point mutations. Fluorescence in situ hybridization confirmed that one of the breakpoints of this inversion mapped to within the RELN gene, and Western blotting revealed an absence of detectable serum reelin protein. Several relatives who were heterozygous for this inversion were neurologically normal and had no signs of psychotic illness. Our findings demonstrate the distinctive phenotype of LCH, which is easily distinguishable from other forms of lissencephaly. Although RELN appears to be critical for normal cerebral and cerebellar development, its role, if any, in the pathogenesis of psychiatric disorders remains unclear. © 2006 Wiley-Liss, Inc.
URI: https://hdl.handle.net/11499/4351
https://doi.org/10.1002/ajmg.b.30392
ISSN: 1552-4841
Appears in Collections:PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Tıp Fakültesi Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

Show full item record



CORE Recommender

SCOPUSTM   
Citations

67
checked on Sep 30, 2024

WEB OF SCIENCETM
Citations

48
checked on Sep 24, 2024

Page view(s)

34
checked on Aug 24, 2024

Google ScholarTM

Check




Altmetric


Items in GCRIS Repository are protected by copyright, with all rights reserved, unless otherwise indicated.