63 research outputs found
Genotype–Phenotype Correlation in DFNB8/10 Families with TMPRSS3 Mutations
In the present study, genotype–phenotype correlations in eight Dutch DFNB8/10 families with compound heterozygous mutations in TMPRSS3 were addressed. We compared the phenotypes of the families by focusing on the mutation data. The compound heterozygous variants in the TMPRSS3 gene in the present families included one novel variant, p.Val199Met, and four previously described pathogenic variants, p.Ala306Thr, p.Thr70fs, p.Ala138Glu, and p.Cys107Xfs. In addition, the p.Ala426Thr variant, which had previously been reported as a possible polymorphism, was found in one family. All affected family members reported progressive bilateral hearing impairment, with variable onset ages and progression rates. In general, the hearing impairment affected the high frequencies first, and sooner or later, depending on the mutation, the low frequencies started to deteriorate, which eventually resulted in a flat audiogram configuration. The ski-slope audiogram configuration is suggestive for the involvement of TMPRSS3. Our data suggest that not only the protein truncating mutation p.T70fs has a severe effect but also the amino acid substitutions p.Ala306Thr and p.Val199Met. A combination of two of these three mutations causes prelingual profound hearing impairment. However, in combination with the p.Ala426Thr or p.Ala138Glu mutations, a milder phenotype with postlingual onset of the hearing impairment is seen. Therefore, the latter mutations are likely to be less detrimental for protein function. Further studies are needed to distinguish possible phenotypic differences between different TMPRSS3 mutations. Evaluation of performance of patients with a cochlear implant indicated that this is a good treatment option for patients with TMPRSS3 mutations as satisfactory speech reception was reached after implantation
Common Molecular Etiologies Are Rare in Nonsyndromic Tibetan Chinese Patients with Hearing Impairment
Background: Thirty thousand infants are born every year with congenital hearing impairment in mainland China. Racial and regional factors are important in clinical diagnosis of genetic deafness. However, molecular etiology of hearing impairment in the Tibetan Chinese population living in the Tibetan Plateau has not been investigated. To provide appropriate genetic testing and counseling to Tibetan families, we investigated molecular etiology of nonsyndromic deafness in this population. Methods: A total of 114 unrelated deaf Tibetan children from the Tibet Autonomous Region were enrolled. Five prominent deafness-related genes, GJB2, SLC26A4, GJB6, POU3F4, and mtDNA 12S rRNA, were analyzed. Inner ear development was evaluated by temporal CT. A total of 106 Tibetan hearing normal individuals were included as genetic controls. For radiological comparison, 120 patients, mainly of Han ethnicity, with sensorineural hearing loss were analyzed by temporal CT. Results: None of the Tibetan patients carried diallelic GJB2 or SLC26A4 mutations. Two patients with a history of aminoglycoside usage carried homogeneous mtDNA 12S rRNA A1555G mutation. Two controls were homozygous for 12S rRNA A1555G. There were no mutations in GJB6 or POU3F4. A diagnosis of inner ear malformation was made in 20.18 % of the Tibetan patients and 21.67 % of the Han deaf group. Enlarged vestibular aqueduct, the most common inner ear deformity, was not found in theTibetan patients, but was seen in 18.33 % of the Han patients. Common molecular etiologies
An Intergenic Non-Coding rRNA Correlated with Expression of the rRNA and Frequency of an rRNA Single Nucleotide Polymorphism in Lung Cancer Cells
METHOD AND APPARATUS FOR QUANTITATIVE NEUTRON ACTIVATION ANALYSIS OF LARGE SAMPLES
A method and apparatus were devised to irradiate multiple samples of large physical size simultaneously in a nonuniform neutron flux. A capsule containing the samples and flux monitors is rotated about an axis at constant speed with samples fixed in a symmetrical geometry so that each position receives the same integrated neutron flux. (auth
Environmental levels of radioactivity in the vicinity of the Lawrence Livermore Laboratory. 1973 annual report
The Lawrence Livermore Laboratory continuously monitors the levels of radioactivity within the Livermore Valley and Site 300. Results of analyses perfomned during 1973 for gross radioactivity and for specific radionuclides of interest in a variety of environmental samples are presented. In all cases, the levels of activity observed during 1973 were found to be below the appropriate concentration guide values in AE C Manual Chapter 0524. Particulate air filters showed gross beta activities lower than those observed during 1972, reflecting a reduction in global fallout in the atmosphere. Gamma spectral measurements on Laboratory perimeter air filters also showed lower activities of global fallout gamma emitters. These perimeter air samples were analyzed for /sup 239/Pu, /sup 236/Pu /sup 90/Sr, /sup 235/U, and /sup 238/U. With the ex ception of one sampling location, the annual average /sup 239/Pu concentration was 1.3 x 10/sup - 17/ mu Ci/ml, typical of global fallout. Air samples taken within Site 300 were analyzed for uranium. These analyses showed a lower than normal ratio of /sup 235/U//sup 238/U. This is due to depleted'' uranium (uranium which is specially processed to lower the /sup 235/U content) used at the Site. Airborne uranium concentrations were well below the standards set by the AEC. Soil samples collected in the off-site vicinity of LLL perimeter boundaries and at Site 300 were analyzed for plutonium, uranium, and gamma emitting radionuclides. Traces of plutonium above global background levels were detected in two off-site samples near the east perimeter of the Laboratory. Sediment samples collected in surface drainage pathways from LLL showed that the plutonium in these sediments was in the same range observed in soil samples collected in the Livermore Valley. Site 300 soil samples indicate depleted levels of /sup 235/U near firing bunkers, but /sup 235/U//sup 236/U rat ios approach that of natural uranium at site perimeters. These data indicate no apparent change from that observed in 1972. Water samples collected within the Livermore Valley exhibited normal background gross beta and tritium activities. Gamma spectral analyses of vegetation samples revealed no gamma-emitting radionuclides other than those present naturally or in global fallout. The vegetation samples collected in areas generally downwind from the Livermore Laboratory revealed tritium activities 10 to 100 times higher than those collected in areas where the Laboratory's contribution should be minimal. However, if the vegetation were a regular pant of one's diet, the annual whole body radiation dose from tritium would be less than 1 mrem. The off- site radiation exposure rates measured by thermoluminescent dosimeters were in the range to be expected from the naturally occurring radionuclides in the soil and from local cosmic radiation. Assessment of the radiation doses to an individual from the observed environmental activities listed indicates the contribution from antificially produced radionuclides is small in comparison with the approximately 100 mrem/y dose received from natural sources. (auth
Radiometrische Untersuchung über die Eignung von Cinchonin als Fällungsreagens für Wolfram und Molybdän
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