LMTK2 Knockout Cell Lysate

We report on complex rearrangements of the 7q21.3 region in a female patient with bilateral split-foot malformation and hearing loss. G-banding karyotype was 46,XX,t(7;15)(q21;q15), t(9;14)(q21;q11.2)dn. By fluorescence, in situ hybridization (FISH), Southern hybridization, and inverse PCR, the 7q21.3 translocation breakpoint was determined at the nucleotide level. The breakpoint did not disrupt any genes, but was mapped to 38-kb telomeric to the DSS1 gene, and 258- and 272-kb centromeric to the DLX6 and DLX5 genes, respectively. It remains possible that the translocation would disrupt the interaction between these genes and their regulatory elements. Interestingly, microarray analysis also revealed an interstitial deletion close to (but not continuous to) the 7q21.3 breakpoint, indicating complex rearrangements within the split-hand/foot malformation 1 (SHFM1) locus in this patient. Furthermore, a 4.6-Mb deletion at 15q21.1-q21.2 adjacent to the 15q15 breakpoint was also identified. Cloning of the deletion junction at 7q21.3 revealed that the 0.8-Mb deletion was located 750-kb telomeric to the translocation breakpoint, encompassing TAC1, ASNS, OCM, and a part of LMTK2. Because TAC1, ASNS, and OCM genes were located on the reported copy number variation regions, it was less likely that the three genes were related to the split-foot malformation. LMTK2 appeared to be a potential candidate gene for SHFM1, but no LMTK2 mutations were found in 29 individuals with SHIM. Further LMTK2 analysis of SHIM patients together with hearing loss is warranted. (C) 2009 Wiley-Liss, Inc.

There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.