Description of mutation spectrum and polymorphism of Wilms' tumor 1 (WT1) gene in hypospadias patients in the Indonesian population.

INTRODUCTION: Hypospadias is one of the most common congenital anomalies of the penis. Previous studies reported mutation of the Wilms' tumor 1 (WT1) gene as a cause of hypospadias. The aim of this study is to describe the WT1 mutation spectrum and polymorphism in hypospadias patients in Indonesia. MATERIAL AND METHODS: DNA was isolated from 74 hypospadias patients at the Division of Pediatric Surgery, Department of Surgery Hasan Sadikin Hospital. All exons in the WT1 gene were amplified by a PCR method, followed by Sanger sequencing. Mutation analysis was performed using BioEdit software and in silico analysis using Mutation Taster, Polymorphism Phenotyping-2 (PolyPhen-2), and Sorting Intolerant from Tolerant (SIFT). RESULT: DNA analysis results showed two types of heterozygous mutations in five subjects (Table), hence the frequency of WT1 mutations was 6.7% (10/148 allele). The first mutation was a missense mutation identified in twin boys. The second was a novel heterozygous alteration in the non-coding region nine bp upstream of exon 6 (c.366-9T>C), which was identified in three patients. One heterozygous polymorphism in the coding region of exon 7 (c.471A>G/rs16754) was identified in 10 subjects. This variant did not cause any change in amino acid products (silence polymorphism). Allele frequency for the G allele (mutant allele) and A allele (wild type) was 13.5% and 86.5%, respectively. DISCUSSION: WT1 is one of the best known hypospadias genes. The WT1 gene is involved in male genital development in the early and late periods of sex determination, and hence is known as a long-term expression gene in genitalia development. Mutation analysis of WT1 in a Chinese population identified that the WT1 mutation frequency was 4.4%. The WT1 mutation frequency identified in the present study was higher, at 6.7%. Coincidentally, research subjects with p.R158H variants were monozygotic twin siblings with midshaft hypospadias accompanied by undescended testis in one and penoscrotal hypospadia with micropenis in the other. The incidence of familial hypospadias in male siblings suffering from hypospadias was reported to be 9.6% in a study conducted by Sorensen et al. Moreover, in the present study polymorphism c.471A>G(rs16754) at exon 7 was identified heterozygously in 10 research subjects (minor allele frequency 13.5%). CONCLUSION: WT1 mutations were identified in only a few cases of hypospadias and most of these were syndromic. This result implies that mutation of WT1 is not a common cause of hypospadias in the Indonesian population.

Carbon nanotube Schottky diode: an atomic perspective.

The electron transport properties of semiconducting carbon nanotube (SCNT) Schottky diodes are investigated with atomic models using density functional theory and the non-equilibrium Green's function method. We model the SCNT Schottky diode as a SCNT embedded in the metal electrode, which resembles the experimental set-up. Our study reveals that the rectification behaviour of the diode is mainly due to the asymmetric electron transmission function distribution in the conduction and valence bands and can be improved by changing metal-SCNT contact geometries. The threshold voltage of the diode depends on the electron Schottky barrier height which can be tuned by altering the diameter of the SCNT. Contrary to the traditional perception, the metal-SCNT contact region exhibits better conductivity than the other parts of the diode.

Investigation of range-energy relationships for low-energy electron beams in silicon and gallium nitride.

The electron beam technique of the Scanning Electron Microscopy (SEM) has been widely used for the characterization of bipolar devices and photodiode materials. The resolution of an electron beam technique is affected by the interaction of the beam and the specimen. The size of this interaction volume, commonly termed the generation volume, is usually characterized by what is called the electron penetration range and is measured from the surface. Since there is currently no consensus on the expressions to use in the calculation of the electron range, this paper provides an analysis of the three most commonly used semiempirical expressions. They are the Gruen range, the universal curve of Everhart and Hoff, and the maximum range of Kanaya and Okayama. This analysis is done using data from the statistical method of Monte Carlo simulations. It was found that the Everhart and Hoff universal curve performs better at low beam energies than the equation of Kanaya and Okayama. However, the validity of all the three expressions is questionable below 5 keV. In order to overcome this, fitted expressions based on the extrapolated range are provided for beam energies below 5 keV in the case of Si and GaN materials. The accuracy of these expressions is affected by the physical parameters used in the Monte Carlo simulations.