12 research outputs found
Coincidence of a Novel KCNJ11 Missense Variant R365H With a Paternally Inherited 6q24 Duplication in a Patient With Transient Neonatal Diabetes
OBJECTIVE—Neonatal diabetes is a heterogeneous group of disorders with diabetes manifestation in the first 6 months of life. The most common etiology in permanent neonatal diabetes is mutations of the ATP-sensitive K+ channel subunits; in transient neonatal diabetes, chromosome 6q24 abnormalities are the most common cause
Multiple adverse thyroid and metabolic health signs in the population from the area heavily polluted by organochlorine cocktail (PCB, DDE, HCB, dioxin)
Abstract Background Several our previous studies showed associations of increasing blood level of persistent organochlorinated pollutants (POPs) with individual thyroid and metabolic adverse health signs in subjects from heavily polluted area (POLL) compared to these from the area of background pollution (BCGR). In this study we present increasing number of subjects with multiple adverse signs positively associated with blood level of polychlorinated biphenyls (PCBs) which is used as a marker of other POPs cocktail. Methods In a total of 2046 adults (834 males and 1212 females; age range 21–75) from POLL and BCGR the serum level of major POPs such as of 15 most abundant PCBs congeners, dichlorodiphenyl-dichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) was estimated by high resolution gas chromatography. In addition, the data on thyroid volume by ultrasound and body mass index were obtained and serum level of thyroperoxidase and thyrotropin receptor antibodies as well as that of free thyroxine, total triiodothyronine, thyrotropin, thyroglobulin, fasting glucose and insulin, cholesterol and triglycerides was measured. Thus, a total of 13 adverse signs were defined and the interrelations between PCBs level and increasing number of subjects with increasing number of adverse signs were evaluated. Results Because of high correlation between major POPs (PCB, DDE and HCB), for this purpose the level of PCBs was considered as a marker also for the presence of DDE and HCB. Thus, if all data obtained from 2046 subjects were stratified according to quintiles of PCBs level, highly significant increase was found (p Conclusion Significantly higher accumulation of adverse signs in subjects with high POPs level was found in POLL thus supporting the conclusion that POPs appear to increase the prevalence of several subclinical and overt thyroid and metabolic disorders.</p
Clinical and biochemical parameters of Slovakian <i>GCK</i> mutation carriers.
<p>Data are presented as median values (range).</p>*<p>Data only available for 35 probands.</p>#<p>Data only available for 33 probands.</p>$<p>For the remaining 32 subjects, diabetes/impaired glucose tolerance was not detected prior to genetic testing.</p><p>BMI = body mass index, HbA1c = glycated hemoglobin A1c, HDL = High Density Lipoprotein, OHA = oral hypoglyceamic agents.</p
<i>GCK</i> mutations identified in Slovakian probands with a phenotype of GCK-MODY.
<p>All sequence information is based on GenBank reference sequence NM_000162.3. Nucleotide numbering reflects cDNA position, with +1 corresponding to the A of the major start codon of exon 1a (present in the pancreatic isoform). Y = yes, N = no.</p
Inhibition of wild type, I436N and L315H glucokinase proteins by human GKRP.
<p>Data are shown as mean ±SEM, and were obtained from 4 independent measurements. Independent t-tests were used to ascertain differences between GKRP-mediated inhibition of both mutants versus that obtained with the wild-type GCK enzyme.</p
MARVELD2 (DFNB49) mutations in the hearing impaired Central European Roma population--prevalence, clinical impact and the common origin.
In the present study we aimed: 1) To establish the prevalence and clinical impact of DFNB49 mutations in deaf Roma from 2 Central European countries (Slovakia and Hungary), and 2) to analyze a possible common origin of the c.1331+2T>C mutation among Roma and Pakistani mutation carriers identified in the present and previous studies.We sequenced 6 exons of the MARVELD2 gene in a group of 143 unrelated hearing impaired Slovak Roma patients. Simultaneously, we used RFLP to detect the c.1331+2T>C mutation in 85 Hungarian deaf Roma patients, control groups of 702 normal hearing Romanies from both countries and 375 hearing impaired Slovak Caucasians. We analyzed the haplotype using 21 SNPs spanning a 5.34Mb around the mutation c.1331+2T>C.One pathogenic mutation (c.1331+2T>C) was identified in 12 homozygous hearing impaired Roma patients. Allele frequency of this mutation was higher in Hungarian (10%) than in Slovak (3.85%) Roma patients. The identified common haplotype in Roma patients was defined by 18 SNP markers (3.89 Mb). Fourteen common SNPs were also shared among Pakistani and Roma homozygotes. Biallelic mutation carriers suffered from prelingual bilateral moderate to profound sensorineural hearing loss.We demonstrate different frequencies of the c.1331+2T>C mutation in hearing impaired Romanies from 3 Central European countries. In addition, our results provide support for the hypothesis of a possible common ancestor of the Slovak, Hungarian and Czech Roma as well as Pakistani deaf patients. Testing for the c.1331+2T>C mutation may be recommended in GJB2 negative Roma cases with early-onset sensorineural hearing loss
Common ancestral haplotypes of Slovak, Hungarian and Czech Romanies, and Pakistani patients.
<p>The haplotypes in Slovak (SK), Czech (CZ), Hungarian (HU) Roma and Pakistani patients with the c.1331+2T>C mutation, and haplotypes in Slovak Roma controls without the c.1331+2T>C mutation. The c.1331+2T>C mutation is shown in bold. The common haplotype is highlighted in light grey.<sup>a</sup>The most similar haplotypes found in 5 out of 56 control individuals. In the remaining 51 control individuals, haplotypes were significantly distinguishable.<sup>b</sup>The haplotype in Pakistani patients with c.1183-1G>A mutation.</p
Cosegregation of haplotypes in a Slovak Roma family (SK5) with DFNB49 related deafness caused by the c.1331+2T>C mutation.
<p>The filled symbol represents the proband with hearing impairment; symbols with dot represent normal hearing carriers. Alleles forming the risk haplotype are shown in grey boxes.</p