Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

Constitutional Haploinsufficiency of Tumor Suppressor Genes in Mentally Retarded Patients With Microdeletions in 17p13.1

2009; Karger Publishers; Volume: 125; Issue: 1 Linguagem: Inglês

10.1159/000218743

1424-8581

Ana Cristina Victorino Krepischi, Diana Rajan, I. Karen Temple, V Shrubb, John A. Crolla, Shuwen Huang, Sarah J. Beal, Paulo Alberto Otto, N. P. Carter, Angela Maria Vianna‐Morgante, Carla Rosenberg,

Genetic factors in colorectal cancer

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 ∼180 kb in 17p13.1. This segment encompasses 18 genes, including 3 involved in cancer, namely <i>KCTD11</i>/<i>REN</i>, <i>DLG4/PSD95,</i> and <i>GPS2</i>. Furthermore, in 2 of the patients, the deletions also included <i>TP53, </i>the most frequently inactivated gene in human cancers. The 3 tumor suppressor genes <i>KCTD11, DLG4, </i>and<i> GPS2, </i>in addition to the <i>GABARAP </i>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 (∼1%) of mental retardation. Further, the constitutive deletion of tumor suppressor genes in these patients, particularly <i>TP53</i>, 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.