Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family.

BACKGROUND: Mutations in TRPV4, a gene that encodes a Ca(2+) permeable non-selective cation channel, have recently been found in a spectrum of skeletal dysplasias that includes brachyolmia, spondylometaphyseal dysplasia, Kozlowski type (SMDK) and metatropic dysplasia (MD). Only a total of seven missense mutations were detected, however. The full spectrum of TRPV4 mutations and their phenotypes remained unclear. OBJECTIVES AND METHODS: To examine TRPV4 mutation spectrum and phenotype-genotype association, we searched for TRPV4 mutations by PCR-direct sequencing from genomic DNA in 22 MD and 20 SMDK probands. RESULTS: TRPV4 mutations were found in all but one MD subject. In total, 19 different heterozygous mutations were identified in 41 subjects; two were recurrent and 17 were novel. In MD, a recurrent P799L mutation was identified in nine subjects, as well as 10 novel mutations including F471del, the first deletion mutation of TRPV4. In SMDK, a recurrent R594H mutation was identified in 12 subjects and seven novel mutations. An association between the position of mutations and the disease phenotype was also observed. Thus, P799 in exon 15 is a hot codon for MD mutations, as four different amino acid substitutions have been observed at this codon; while R594 in exon 11 is a hotspot for SMDK mutations. CONCLUSION: The TRPV4 mutation spectrum in MD and SMDK, which showed genotype-phenotype correlation and potential functional significance of mutations that are non-randomly distributed over the gene, was presented in this study. The results would help diagnostic laboratories establish efficient screening strategies for genetic diagnosis of the TRPV4 dysplasia family diseases.

Percutaneous transluminal coronary angioplasty for morphologic left anterior descending artery lesion in a patient with dextrocardia. A case report and literature review.

A case report of percutaneous transluminal coronary angioplasty (PTCA) to treat coronary atherosclerotic lesions in a patient with dextrocardia associated with situs inversus totalis is presented. The patient was a sixty-two-year-old man who was admitted with a diagnosis of congestive heart failure. Cardiac catheterization was performed. Left ventriculography showed mild hypokinesis in segments 2 and 3 with ejection fraction of 63%. Coronary arteriography revealed 74% stenosis in segment 7 of the left anterior descending (LAD) artery. PTCA for this lesion was performed. Successful dilation was achieved with the residual stenosis in the LAD reduced from 74% to 34%. Performance of PTCA in patients with dextrocardia is extremely rare, and only 8 cases have been reported to date. However, by visualizing the procedure as a mirror image and choosing a guide catheter that permits good engagement, it appears possible to perform it like ordinary PTCA.

Unusual right coronary artery runoff with right and left main coronary artery aneurysm. A case report.

A rare case of unusual right coronary artery runoff with right and left main coronary artery aneurysm is presented. The discussion is mainly from the etiologic point of view.

Phylogenetic analysis of the Erysipelothrix rhusiopathiae and Erysipelothrix tonsillarum based upon 16S rRNA.

The nucleotide sequences of 16S rRNA genes of Erysipelothrix rhusiopathine and Erysipelothrix tonsillarum were determined. The sequences are almost similar (99.8%) with only three nucleotides mismatched.

Reaction of hydroxyapatite-sol in bone marrow.

Hydroxyapatite-sol was prepared by dispersing hydroxyapatite microcrystals into saline. The hydroxyapatite microcrystals were synthesized by neutralization reaction of calcium hydroxide suspension and phosphoric acid solution. Sizes of the hydroxyapatite microcrystals were less than 0.1 microns, and the mean value was 0.05 microm. The 0.2 ml hydroxyapatite-sol with a concentration of 14.8 mg/ml was injected into medullary cavities of rat femurs. Both sintered hydroxyapatite powder suspension and saline as comparative materials were injected into the medullary cavities in the same way. Reaction of the hydroxyapatite-sol in the bone medullary cavities was investigated histologically using light and transmission electron microscopes. After 3 days, new bone formation was observed by injection of hydroxyapatite-sol, while no bone formation was observed by injection of sintered hydroxyapatite powder and saline. Osteoblasts were observed endocytosing the hydroxyapatite-sol in the medullary cavities of the rats. Macrophages and undifferentiated osteoblasts were found around the hydroxyapatite-sol aggregation by transmission electron microscope. After 5 days, amounts of new bone increased and matured, forming trabeculae. Many osteoblasts were observed in a line along the surface of the bone. On the other hand, 5 days after injection of sintered hydroxyapatite powder and saline to bone formation was observed while at 10 days after injection, some immature new bone formation started to be observed. New bone increased and matured at 15 days postoperatively. From these results, it was concluded that hydroxyapatite-sol only quickly promotes the formation of new bone in bone marrow and can be used as injection liquid of new biomaterials for bone formation.