PTPRF is disrupted in a patient with syndromic amastia

<p>Abstract</p> <p>Background</p> <p>The presence of mammary glands distinguishes mammals from other organisms. Despite significant advances in defining the signaling pathways responsible for mammary gland development in mice, our understanding of human mammary gland development remains rudimentary. Here, we identified a woman with bilateral amastia, ectodermal dysplasia and unilateral renal agenesis. She was found to have a chromosomal balanced translocation, 46,XX,t(1;20)(p34.1;q13.13). In addition to characterization of her clinical and cytogenetic features, we successfully identified the interrupted gene and studied its consequences.</p> <p>Methods</p> <p>Characterization of the breakpoints was performed by molecular cytogenetic techniques. The interrupted gene was further analyzed using quantitative real-time PCR and western blotting. Mutation analysis and high-density SNP array were carried out in order to find a pathogenic mutation. Allele segregations were obtained by haplotype analysis.</p> <p>Results</p> <p>We enabled to identify its breakpoint on chromosome 1 interrupting the <it>protein tyrosine receptor type F gene </it>(<it>PTPRF</it>). While the patient's mother and sisters also harbored the translocated chromosome, their non-translocated chromosomes 1 were different from that of the patient. Although a definite pathogenic mutation on the paternal allele could not be identified, <it>PTPRF</it>'s RNA and protein of the patient were significantly less than those of her unaffected family members.</p> <p>Conclusions</p> <p>Although <it>ptprf </it>has been shown to involve in murine mammary gland development, no evidence has incorporated <it>PTPRF </it>in human organ development. We, for the first time, demonstrated the possible association of <it>PTPRF </it>with syndromic amastia, making it a prime candidate to investigate for its spatial and temporal roles in human breast development.</p

Chemistry and Interconversion of Complex Trichothecenes

The trichothecenes are a ubiquitous group of toxic fungal sesquiterpenoids. Previous studies have shown that the 12,13-epoxide present in the trichothecenes may be crucial for biological activity. To gain further insight into the biological role of the epoxide, successful employment of the Sharpless deoxygenation protocol has been achieved after extensive model studies. This procedure gave the 12,13-exomethylene compounds (119) and (121) from the corresponding epoxytrichothecenes, namely triacetoxyscirpene (63) and triacetyldeoxynivalenol (120). In an extension to this work, Sharpless deoxygenation furnished the key intermediate, olefin (124), which was used to synthesise the 12,13-epi-epoxytrichothecene (128) via ozonolysis and reaction of the derived norketone (125) with dimethylsulphonium methylide. Both the Sharpless deoxygenation product (119) and the epi-epoxytrichothecene (128) were found to be essentially non-toxic, thus demonstrating for the first time the necessary presence of the epoxide and its stereochemical definition. Further work has led to methodology for the provision of less readily available trichothecenes. To this end, deoxynivalenol (23) has been successfully synthesised from one of our culture products, anguidine (9), via another naturally occurring trichothecene, calonectrin (5). This methodology involved selective removal of the C-4 oxygen functionality, selective allylic oxidation at C-8, to establish the enone system, and introduction of the C-7 hydroxyl moiety