Constitutional haploinsufficiency of tumor suppressor genes in mentally retarded patients with microdeletions in 17p13.1.

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.

Isolated imprinting mutation of the DLK1/GTL2 locus associated with a clinical presentation of maternal uniparental disomy of chromosome 14.

The clinical phenotypes of maternal and paternal uniparental disomy of chromosome 14 (UPD14) are attributed to dysregulation of imprinted genes. A large candidate locus exists within 14q32, under the regulation of a paternally methylated intergenic differentially methylated region (IG-DMR). We present a patient with clinical features of maternal UPD14, including growth retardation, hypotonia, scoliosis, small hands and feet, and advanced puberty, who had loss of methylation of the IG-DMR with no evidence of maternal UPD14. This case provides support for the hypothesis that the maternal UPD14 phenotype is due to aberrant gene expression within the imprinted domain at 14q32.

Isolated imprinting mutation of the DLK1/GTL2 locus associated with a clinical presentation of maternal uniparental disomy of chromosome 14.

The clinical phenotypes of maternal and paternal uniparental disomy of chromosome 14 (UPD14) are attributed to dysregulation of imprinted genes. A large candidate locus exists within 14q32, under the regulation of a paternally methylated intergenic differentially methylated region (IG-DMR). We present a patient with clinical features of maternal UPD14, including growth retardation, hypotonia, scoliosis, small hands and feet, and advanced puberty, who had loss of methylation of the IG-DMR with no evidence of maternal UPD14. This case provides support for the hypothesis that the maternal UPD14 phenotype is due to aberrant gene expression within the imprinted domain at 14q32.

Opinion statement on the minimal acceptable standards of healthcare in cerebral palsy.

PURPOSE: Recent studies have shown a marked variation in the standards of healthcare for young people with disabilities in different regions of the UK and even within the same health district. Equity in the provision of healthcare is a fundamental principle of the NHS. However, this can only be measured against an agreed minimal standard of healthcare that serves as a benchmark for healthcare purchasers and providers. The aim of the present document is to develop a set of minimum standards of healthcare for children and adults with cerebral palsy (CP). METHODS: The document was developed in two stages by a multi-professional and multi-disciplinary group of practitioners in the field of CP. Initially, members of the panel jointly formulated a statement of what they believed should be the minimal acceptable standards of healthcare in CP drawing on their own experience and the published scientific evidence. In the second stage the views of some of the relevant professional bodies and voluntary organizations on the draft statement were sought. The responses of these organizations were incorporated into the final document if agreed by the panel. RESULTS AND CONCLUSIONS: Twenty-two recommendations were made. These were considered the minimum standards of care in a district general hospital. The emphasis was on the organisation and delivery of healthcare for children with CP. The statement is intended to stimulate debate especially in relation to the equity of service provision throughout the country and may be used to inform purchasers of healthcare. Similarly, it may also be useful to providers of healthcare as an audit tool.

Chronic bullous disease of childhood--another cause for potential misdiagnosis of sexual abuse?

There have been several reports of unusual skin conditions producing genital lesions that can be mistaken for sexual abuse. We report on another unusual skin condition, well known to dermatologists, that can again lead to potential misdiagnosis of sexual abuse.