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Microdeletions spanning 2p14-p15 have recently been described in two patients with developmental and speech delay and intellectual disability but no congenital malformations or severe facial dysmorphism. We report a 4-year-old boy with a de novo 3.7 Mb long deletion encompassing the region deleted in the previous cases. The patient had clinical features partly consistent with the published cases including intellectual disability, absent speech, microcephaly, long face, bulbous nasal tip and thin upper lip, but his overall clinical picture was more severe compared to the published patients. The identification of this additional patient and a detailed analysis of deletions identified in various patient cohorts and in normal individuals support the existence of a new rare microdeletion syndrome in 2p14-p15. Its critical region is in the vicinity of but clearly separate from the minimal region deleted in the well established 2p15-p16.1 microdeletion syndrome. A thorough comparison of the deletions and phenotypes indicates that multiple genes located in this region may be involved in intellectual functioning, and that some patients may show composite and more complex phenotypes due to deletions spanning both critical regions., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We identified a missense germline mutation (Gly245Ser) in one of the mutation hot spots of the TP53 gene in two affected members of a Li-Fraumeni syndrome family. We also analyzed their tumors, a liposarcoma and a colorectal carcinoma. Both tumors exhibited p53 protein accumulation but none of them showed loss of the wild-type allele of the TP53 gene. We reviewed all published cases of tumors in germline TP53 mutation carriers where loss of heterozygosity data were available and identified 84 tumors with loss of the wild-type allele, 57 tumors with retention of heterozygosity, and 9 tumors with loss of the allele harboring the germline mutation. Among the tumors showing p53 accumulation, we observed a significant difference in the fraction of tumors showing p53 protein accumulation between the tumors with loss of the wild-type allele and those with retention of TP53 heterozygosity. This supports the idea that the pathogenesis of tumors in germline TP53 mutation carriers does not have to be associated with loss of the wild-type TP53 allele. The product of the normal allele can potentially be inactivated by a variety of other mechanisms or, as suggested by the analysis, many of these tumors may even preserve the activity of the wild-type p53 protein.