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Constitutional haploinsufficiency of tumor suppressor genes in mentally retarded patients with microdeletions in 17p13.1.
- Source :
-
Cytogenetic and genome research [Cytogenet Genome Res] 2009; Vol. 125 (1), pp. 1-7. Date of Electronic Publication: 2009 Jul 14. - Publication Year :
- 2009
-
Abstract
- Chromosome microdeletions or duplications are detected in 10-20% of patients with mental impairment and normal karyotypes. A few cases have been reported of mental impairment with microdeletions comprising tumor suppressor genes. By array-CGH we detected 4 mentally impaired individuals carrying de novo microdeletions sharing an overlapping segment of approximately 180 kb in 17p13.1. This segment encompasses 18 genes, including 3 involved in cancer, namely KCTD11/REN, DLG4/PSD95, and GPS2. Furthermore, in 2 of the patients, the deletions also included TP53, the most frequently inactivated gene in human cancers. The 3 tumor suppressor genes KCTD11, DLG4, and GPS2, in addition to the GABARAP gene, have a known or suspected function in neuronal development and are candidates for causing mental impairment in our patients. Among our 4 patients with deletions in 17p13.1, 3 were part of a Brazilian cohort of 300 mentally retarded individuals, suggesting that this segment may be particularly prone to rearrangements and appears to be an important cause (approximately 1%) of mental retardation. Further, the constitutive deletion of tumor suppressor genes in these patients, particularly TP53, probably confers a significantly increased lifetime risk for cancer and warrants careful oncological surveillance of these patients. Constitutional chromosome deletions containing tumor suppressor genes in patients with mental impairment or congenital abnormalities may represent an important mechanism linking abnormal phenotypes with increased risks of cancer.<br /> (Copyright 2009 S. Karger AG, Basel.)
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Adolescent
Apoptosis Regulatory Proteins
Cell Cycle Proteins
Child
Child, Preschool
Chromosome Mapping
Comparative Genomic Hybridization
Disks Large Homolog 4 Protein
Female
Gene Dosage
Genes, p53
Humans
In Situ Hybridization, Fluorescence
Intracellular Signaling Peptides and Proteins genetics
Male
Membrane Proteins genetics
Microtubule-Associated Proteins genetics
Phenotype
Potassium Channels genetics
Transferases
Chromosome Deletion
Chromosomes, Human, Pair 17 genetics
Genes, Tumor Suppressor
Intellectual Disability genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1424-859X
- Volume :
- 125
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cytogenetic and genome research
- Publication Type :
- Academic Journal
- Accession number :
- 19617690
- Full Text :
- https://doi.org/10.1159/000218743