Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene
ABSTRACT Mutations of the WFS1 gene have been implicated in autosomal dominant diseases, such as low-frequency sensorineural hearing impairment (LFSNHI) and/or diabetes mellitus and/or optic atrophy. The aim was to investigate WFS1 gene sequences in a family with diabetes mellitus and hearing impairment.
Three members of a family with a maternally inherited combination of diabetes mellitus and hearing impairment, but no specific mutations in its mitochondrial genome, were investigated for mutations in the WFS1 gene.
This pedigree, in which the proband had non-insulin-dependent diabetes mellitus and congenital hearing impairment and his mother a triple combination of diabetes mellitus, hearing impairment and optic atrophy, was found to be associated with autosomal dominant transmission of the E864K mutation of the WFS1 gene.
In the light of this confirmatory study, we recommend the systematic analysis of WFS1 gene sequences in patients with parentally inherited diabetes mellitus and deafness (+/- optic atrophy), in particular when diabetogenic mtDNA mutations have been excluded.
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ABSTRACT: This paper reports on a new type of system configuration that allows for multiplexed operation of Ultrasonic Motors (USM). This system consists of a control board and a multiplexer board paired with each USM. The control signal from the controller board sends an address signal to the multiplexer board to enable or disable the ground return link for the motor. The piezo-deflection amplitude from the addressed USM is then connected to the controller board. Each motor is connected in parallel with the power bus. The controller board consists of a microcontroller, a field programmable gate array, a digital frequency synthesizer, a push-pull converter and a hardware interface that allows the user to change control parameters through a LABVIEW graphic user interface. Experimental results confirm that the strategy allows the user to control a number of Shinsei USM60 ultrasonic motors in a sequential fashion.Applied Power Electronics Conference and Exposition, 2004. APEC '04. Nineteenth Annual IEEE; 02/2004
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ABSTRACT: Wolfram syndrome (WS) is a rare, progressive, neurodegenerative disorder with an autosomal recessive pattern of inheritance. The gene for WS, WFS1, was identified on chromosome 4p16 and most WS patients carry mutations in this gene. However, some studies have provided evidence for genetic heterogeneity and the genotype-phenotype relationships are not clear. Our aim was to ascertain the spectrum of WFS1 mutations in Brazilian patients with WS and to examine the phenotype-genotype relationships in these patients. Clinical characterization and analyses of the WFS1 gene were performed in 27 Brazilian patients with WS from 19 families. We identified 15 different mutations in the WFS1 gene in 26 patients, among which nine are novel. All mutations occurred in exon 8, except for one missense mutation which was located in exon 5. Although we did not find any clear phenotype-genotype relationship in patients with mutations in exon 8, the homozygous missense mutation in exon 5 was associated with a mild phenotype: onset of diabetes mellitus and optic atrophy during adulthood with good metabolic control being achieved with low doses of sulfonylurea. Our data show that WFS1 is the major gene involved in WS in Brazilian patients and most mutations are concentrated in exon 8. Also, our study increases the spectrum of WFS1 mutations. Although no clear phenotype-genotype relationship was found for mutations in exon 8, a mild phenotype was associated with a homozygous missense mutation in exon 5.European Journal of Endocrinology 12/2008; 160(2):309-16. DOI:10.1530/EJE-08-0698 · 3.69 Impact Factor
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ABSTRACT: Implant treatment is an attractive substitute to traditional fixed/removable prosthetic appliances. In patients with diabetes, dental implant therapy has been considered a contraindication. Hyperglycemia augments the severity of periodontal disease, and glycemic control is an essential variable in determining the success of dental implants in subjects with diabetes. Subjects with well-controlled diabetes may not be significantly compromised and can have high dental implant success rates compared to individuals with poorly controlled diabetes. The focused questions addressed in this systematic review were as follows: Can patients with diabetes be good candidates for dental implant therapy? And how does hyperglycemia and glycemic control influence osseointegration? A systematic literature search of MEDLINE/PubMed articles published from 1982 up to and including July 2009 was independently performed by two investigators. In addition, reference lists of original and review articles were searched. The search strategy was to use the following terms in different combinations: dental implants, immediate implants, osseointegration, periodontal disease, diabetes, hyperglycemia, metabolic control, and glycemic control. The search included studies on humans and diabetes-induced animal models. The selection criteria included all levels of available evidence. Suitable variables included the implant survival rate among individuals with diabetes, effects of hyperglycemia and glycemic control on bone, and maintenance of dental implants in subjects with diabetes. Articles published only in the English language were considered, and unpublished data were not sought. We initially identified 33 studies. Fifteen studies, which did not fulfill the selection criteria, were excluded. The included studies reported that poorly controlled diabetes negatively affects implant osseointegration; however, under optimal serum glycemic control, osseointegration can successfully occur in patients with diabetes. Animal studies have confirmed that osseointegration can be successfully achieved in insulin-controlled rats with diabetes, whereas in uncontrolled rats with diabetes, the bone-to-implant contact appears to decrease with time. The use of antiseptic mouthrinses and oral-hygiene maintenance helps in achieving a successful dental implant osseointegration in subjects with diabetes. A successful dental implant osseointegration can be accomplished in subjects with diabetes with good metabolic control (serum glycemic level and hemoglobin A1c in normal range) in a similar manner as in subjects without diabetes.Journal of Periodontology 11/2009; 80(11):1719-30. DOI:10.1902/jop.2009.090283 · 2.57 Impact Factor