Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Immunohistochemical analysis of TrkA neurotrophin receptor expression in human non-neuronal carcinomas

The Trk family of tyrosine protein kinase receptors plays a significant role in the development and maintenance of neural tissues. It has been recently shown that Trk receptors are also expressed by a wide range of normal non-neuronal tissues in humans in a cell type-specific manner. In the present study, the expression patterns of TrkA in 337 non-neuronal invasive carcinomas of 15 different human tissues were investigated immunohistochemically. Overall, 133 (39%), 101 (30%) and 103 (31%) tumors exhibited strong, moderate and no TrkA Immunoreactivity, respectively. Esophageal and thyroid carcinomas expressed high levels of TrkA, whereas the levels in gastric and colon cancers were low. TrkA expression was detected not only in carcinomas originating from TrkA-positive normal counterpart tissues, Including the esophagus, breast, lung and uterus, but also in those from TrkA-negative tissues/cells of the thyroid, liver and ovary. Immunostaining for nerve growth factor-β, the specific ligand for TrkA, in esophageal and breast carcinomas demonstrated its immunoreactivity in stromal fibroblasts and some TrkA-expressing tumor cells. These results suggest that paracrine/autocrine regulation via stromal/tumoral NGF-tumoral TrkA interaction may be involved In the growth of certain non-neuronal carcinomas.     

Prenatal diagnosis of Werdnig Hoffmann disease in China

Objective To establish a means for prenatal prediction of spinal muscular atrophy (SMA) through survival motor neuron (SMN) gene deletion analysis and genetic counseling in families with a child affected with SMA.
Methods Genetic analysis for prenatal prediction of Werdnig-Hoffmann disease was performed in a at risk Chinese family by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) in SMN gene exons 7 and 8.
Results The pregnancy was positive for the homozygous deletion of the SMN gene, thus the fetus was diagnosed as being affected and the pregnancy was terminated.
Conclusion This approach is fast and reliable for DNA-based prenatal diagnosis of Werdnig-Hoffmann disease.     

Q-Switched Alexandrite Laser Therapy for Pigmentation of the Lips Owing to Laugier-Hunziker Syndrome

BACKGROUND: Laugier-Hunziker (LH) syndrome is a rare benign condition in which hyperpigmentation of the lips and buccal mucosa occurs with no systemic associations. OBJECTIVE: We report the response to treatment with the Q-switched alexandrite laser (QSAL) because there are few reports on therapy for LH syndrome. METHODS: The QSAL was used for pigmentation of the lips in a 63-year-old woman with LH syndrome. Laser irradiation was done at 5.0 J/cm2 with a 3 mm spot size. RESULTS: There was 100% clearance of pigmentation of the lips with a single laser treatment, and recurrence was not observed after 6 months. CONCLUSION: The QSAL is very effective for pigmentation owing to LH syndrome.