Journal article
Refinement of a 400-kb Critical Region Allows Genotypic Differentiation between Isolated Lissencephaly, Miller-Dieker Syndrome, and Other Phenotypes Secondary to Deletions of 17p13.3
American journal of human genetics, v 72(4), pp 918-930
Apr 2003
PMID: 12621583
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Deletions of 17p13.3, including the LIS1 gene, result in the brain malformation lissencephaly, which is characterized by reduced gyration and cortical thickening; however, the phenotype can vary from isolated lissencephaly sequence (ILS) to Miller-Dieker syndrome (MDS). At the clinical level, these two phenotypes can be differentiated by the presence of significant dysmorphic facial features and a more severe grade of lissencephaly in MDS. Previous work has suggested that children with MDS have a larger deletion than those with ILS, but the precise boundaries of the MDS critical region and causative genes other than LIS1 have never been fully determined. We have completed a physical and transcriptional map of the 17p13.3 region from LIS1 to the telomere. Using fluorescence in situ hybridization, we have mapped the deletion size in 19 children with ILS, 11 children with MDS, and 4 children with 17p13.3 deletions not involving LIS1. We show that the critical region that differentiates ILS from MDS at the molecular level can be reduced to 400 kb. Using somatic cell hybrids from selected patients, we have identified eight genes that are consistently deleted in patients classified as having MDS. In addition, deletion of the genes CRK and 14-3-3ɛ delineates patients with the most severe lissencephaly grade. On the basis of recent functional data and the creation of a mouse model suggesting a role for 14-3-3ɛ in cortical development, we suggest that deletion of one or both of these genes in combination with deletion of LIS1 may contribute to the more severe form of lissencephaly seen only in patients with MDS.
Metrics
Details
- Title
- Refinement of a 400-kb Critical Region Allows Genotypic Differentiation between Isolated Lissencephaly, Miller-Dieker Syndrome, and Other Phenotypes Secondary to Deletions of 17p13.3
- Creators
- Carlos Cardoso - University of ChicagoRichard J. Leventer - University of ChicagoHeather L. Ward - University of ChicagoKazuhito Toyo-oka - University of California San DiegoJune Chung - University of ChicagoAlyssa Gross - University of ChicagoChrista L. Martin - University of ChicagoJudith Allanson - Children's Hospital of Eastern OntarioDaniela T. Pilz - University Hospital of WalesAnn H. Olney - University of Nebraska Medical CenterOsvaldo M. Mutchinick - Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránShinji Hirotsune - Saitama Medical UniversityAnthony Wynshaw-Boris - University of California San DiegoWilliam B. Dobyns - University of ChicagoDavid H. Ledbetter - University of Chicago
- Publication Details
- American journal of human genetics, v 72(4), pp 918-930
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000181972600012
- Scopus ID
- 2-s2.0-0037385481
- Other Identifier
- 991020100054304721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Genetics & Heredity