Report of a new mutation and frequency of connexin 26 gene (GJB2) mutations in patients from three provinces of Iran

Autosomal recessive and sporadic non-syndromic hearing loss (ARSNSHL) is the major form of hereditary deafness. Mutations in the GJB2 gene encoding the gap-junction protein Connexin 26 have been identified to be highly associated with ARSNSHL. In this study we have analyzed 196 deaf subjects from 179 families having one or more deaf children in 3 proviences of Iran, including Kordestan, Khuzestan and Golestan. The nested PCR prescreening strategy and direct sequencing technique were used to detect the mutations in coding exon of the gene. Altogether 3 GJB2 recessive mutations including 35delG, 167delT and V27I+E114G, were identified in 23 of 179 families (12.8). Fourteen of 179 families were observed to have GJB2 mutation in both alleles (7.8). A novel variant (R159H) also was found in a deaf family from Khuzestan. Four polymorphisms V27I, E114G, S86T and V153 I also were detected in 7 families. A polymorphism(S86T) was seen in the whole population studied. Our data indicated that the rate of connexin 26 mutations is different in this three Irainian population and is lower than the high frequency of 35delG (26) reported from Gilan province in the north of Iran

Frequency of a very rare 35delG mutation in two ethnic groups of Iranian populations

The 35delG mutation in the Connexin 26 gene (Cx26), at the DNFB1 locus is the most common mutation in the patients with autosomal recessive non-syndromic hearing loss (ARNSHL). We have studied a total of 224 deaf cases from 189 families in two populations of Iran (Sistan va Bluchestan and Hormozgan provinces) by prescreening nested PCR, polyacrylamide gel electrophoresis and consequent direct sequencing method for all cases. The aim of the present work was to find prevalence of GJB2 mutations in the populations studied. Four different GJB2 mutations including 35delG, W24X, R127H and (V27I + E114 G) were identified in 11 of 189 families (5.8). Two polymorphisms (V27I and V153I) also were detected in 14 families. A polymorphism S86T was determined in all cases. Homozygote 35delG mutation was found only in 1 of 189 families (0.5).The rate of Cx26 mutations found in this study was lower than other Iranian populations. So the cause of deafness in the populations studied remains to be detected in other loci or genes. © 2014, Iranian Journal of Public Health. All rights reserved

Mutation analysis of GJB2 and GJB6 genes and the genetic linkage analysis of five common DFNB loci in the Iranian families with autosomal recessive non-syndrom

The incidence of pre-lingual hearing loss (HL) is about 1 in 1000 neonates. More than 60% of cases are inherited. Non-syndromic HL (NSHL) is extremely heterogeneous: more than 130 loci have been identified so far. The most common form of NSHL is the autosomal recessive form (ARNSHL). In this study, a cohort of 36 big ARNSHL pedigrees with 4 or more patients from 7 provinces of Iran was investigated. All of the families were examined for the presence of GJB2 and GJB6 (del D13S1830 and del D13S1854) mutations using direct sequencing and multiplex PCR methods, respectively. The negative pedigrees for the above-named genes were then tested for the linkage to 5 known loci including DFNB3 (MYO7A), DFNB4 (SLC26A4), DFNB7/11 (TMC1), DFNB21 (TECTA) and DFNB59 (PJVK) by genotyping the corresponding STR markers using PCR and PAGE. Six families had GJB2 mutations. No GJB6 mutation was found. Totally, 3 families showed linkage to DFNB4, 1 family to DFNB7/11 and 1 family to DFNB21. No family was linked to DFNB59. GJB2 included 16.6% of the causes of ARNSHL in our study. In the remaining negative families, DFNB4 accounted for 10% of the causes. Other loci including DFNB7/11 and DFNB21 were each responsible for 3.3% of the etiology. Thus, DFNB1(GJB2) and DFNB4 are the main causes of ARNSHL in our study and GJB6 mutations (del D13S1830, del D13S1854), DFNB3 and DFNB59 were absent. Totally, 30.5% of the ARNSHL etiology was found in this study

Frequencies of mutations in the connexin 26 gene (GJB2) in two populations of Iran (Tehran and Tabriz)

While hearing loss has been considered to be a very heterogeneous disorder, mutations in Gap junction beta 2 (GJB2) gene encoding Connexin 26 (Cx26) protein are the major cause of autosomal recessive and sporadic non-syndromic deafness in many populations. In this study, we have investigated the prevalence of the GJB2 gene mutations using nested PCR pre screening strategy and direct sequencing method. Two hundred and seventy two hearing impaired subjects were studied from 210 families obtained from two large cities of Iran (Tehran and Tabriz). Twenty four different genetic variants were identified. Cx26 mutations were found in 53 of the 210 families (25.2) including T8M, 35delG, W24X, R32H, V371, E47X, 167delT, delE120, Y136X, R143W, R184P, 235delC and V27I+E114G. Homozygosity and compound heterozygosity for the Cx26 mutations were found in 39 of 210 (18.5) families. Homozygosity for the 35delG mutation was the most common that causes hearing loss in 28 (13.3) patients. Six novel variants H16R, E101E, K102Q, G200R, 327delG and G130A were detected in this study. As a conclusion, the present survey revealed that the rate of mutation in Cx26 gene in our area is lower than in Europe; nevertheless, this rate is regarded as a considerable cause of deafness in the cited provinces in Iran

Autosomal recessive and sporadic non syndromic hearing loss and the incidence of Cx26 mutations in a province of Iran

Despite the enormous heterogeneity of genetic hearing loss, mutations in the GJB2 (connexin 26) gene located on "DFNB1" locus (13q12) account for up to 50 of cases of autosomal recessive non-syndromic hearing loss (ARNSHL) in some populations. This study describes the analysis of 100 autosomal recessive and sporadic nonsyndromic hearing loss individuals from 79 families each having at least one deaf child in Chehar Mahal va Bakhtiari province in west of Iran. We have investigated the prevalence of the connexin 26 gene mutations using nested PCR strategy to screen the predominant 35delG mutation and subsequent direct sequencing to detect other Cx26 mutations. Seven different genetic variants were detected from which one novel variant was including 363delC. The 35delG was the most common mutation found in 5 of 79 families (6.3). Cx26 related deafness mutations (35delG,V27I; E114G) and R127H) were found in 12 of 158 chromosomes studied (7.8%). We conclude that the association of Cx26 mutations with deafness in Chehar Mahal va Bakhtiari province is low and looks like most other populations of Iran

COMPARATIVE ACTIVITIES OF PHENYLALANINE AMMONIA-LYASE AND TYROSINE AMMONIA-LYASE AND PHENOLIC COMPOUNDS ACCUMULATED IN CASSAVA ELICITED CELL

Plants respond to attack by pathogens by initiating a change in cellular metabolism, leading to synthesis of antifungal proteins, production of phytoalexins and/or accumulation of phenolic compounds, namely lignins and salicylic. Lignins reinforce pectocellulosic cell walls and limit the invasion of plant tissues by pathogens; while salicylic acid plays a role in signals plant defense against pathogens. The objective of this study was to evaluate the activities of phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) and tyrosine ammonia-lyase (TAL, EC 4.3.1.5); and to determine the level of their involvement in the biosynthetic pathway of these phenylpropanoids in cells of cassava ( Manihot esculenta Crantz, cv Yac\ue9) elicited with salicylic acid (SA). PAL and TAL activities were demonstrated in crude extract enzyme. PAL activity was 9.8 times greater than that of TAL in the pellet obtained with 20% (w/v) ammonium sulphate. In the extract treated with Dowex 2 (cationic), TAL activity was 36.7 times greater than that of PAL. pH and temperature optima of PAL (8; 40\ub0 C) differed from those of TAL (8.5; 30\ub0 C). In the presence of SA, PAL and TAL activities were respectively maximum 24 and 72 hr after inoculation. TAL activity and induced phenols were much higher than PAL. PAL and TAL activities were optimised respectively, by 75 and 100 \u3bcM of SA. The synthesis of phenolic compounds was concomitant with enzymes stimulation. These results show that PAL is different from TAL and the two enzymes are involved in the biosynthetic pathway of phenylpropanoids in cassava.Les plantes r\ue9pondent \ue0 l\u2019attaque des pathog\ue8nes par l\u2019initiation d\u2019un changement du m\ue9tabolisme cellulaire, conduisant \ue0 la synth\ue8se des prot\ue9ines antifongiques, la production des phytoalexines et/ou l\u2019accumulation des compos\ue9s ph\ue9noliques appel\ue9s lignines et salicyliques. Les lignines renforcent les membranes cellulaires p\ue9ctocellulosiques et limitent l\u2019invasion des tissues des plantes par les pathog\ue8nes, alors que l\u2019acide salicylique joue un r\uf4le dans les signaux de d\ue9fense des plantes contre les pathog\ue8nes. Cette \ue9tude avait pour objectif d\u2019\ue9valuer les activit\ue9s du phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) et du tyrosine ammonia-lyase (TAL, EC 4.3.1.5) ainsi que de d\ue9terminer le niveau de leur implication dans la voie biosynth\ue9tique de ces ph\ue9nylpropanoides dans les cellules de manioc ( Manihot esculenta Crantz, cv Yac\ue9) dues \ue0 l\u2019acide salicylic. Les activit\ue9s PAL et TAL \ue9taient d\ue9montr\ue9es dans un extract de base d\u2019enzyme. L\u2019activit\ue9 PAL \ue9tait 9.8 fois plus \ue9lev\ue9e que celle de TAL dans la boulette obtenue du sulfate d\u2019ammonium (w/v) 20%. Dans l\u2019extract trait\ue9 avec Dowex 2 (cationique), l\u2019activit\ue9 TAL \ue9tait 36.7 fois plus \ue9lev\ue9e que celle du PAL. Le pH et la temp\ue9rature optima de PAL (8; 40\ub0 C) diff\ue9raient de ceux du TAL (8.5; 30\ub0 C). En pr\ue9sence de l\u2019acide salicylique, les activit\ue9s PAL et TAL \ue9taient respectivement maximum \ue0 24 et 72 heures apr\ue8s inoculation. L\u2019activit\ue9 TAL ainsi que les ph\ue9nols induits \ue9taient plus \ue9lev\ue9s que PAL. Les activit\ue9s PAL et TAL \ue9taient plus optimis\ue9es respectivement par 75 et 100 \u3bcM de l\u2019acide salicylique. La synth\ue8se des compos\ue9s ph\ue9noliques \ue9tait concomitante avec la stimulation enzymatiques. Ces r\ue9sultats montrent que PAL est diff\ue9rent de TAL et les deux enzymes sont impliqu\ue9s dans la voie biosynth\ue9tique des ph\ue9nylpropano\ubfdes dans le manioc

Risk factor investigation for cardiovascular health through WHO STEPS approach in Ardabil, Iran

Objectives: Reliable evidence is the keystone for any noncommunicable disease (NCD) prevention plan to be initiated. In this study we carried out a risk factor investigation based on the WHO Stepwise approach to Surveillance (STEPS). Methods: The study was conducted on 1000 adults between 15 and 64 years of age living in Ardabil province, north-west Iran during 2006, based on the WHO STEPS approach to surveillance of risk factors for NCD. At this stage only the first and second steps were carried out. Data were collected through standard questionnaires and methods analyzed using STATA version 8 statistical software package. Results: 29.0% of men and 2.6% of women were current daily tobacco smokers. The mean number of manufactured cigarettes smoked per day was 18.9 among current daily smokers. Smoking was most prevalent among men of low-income families and those of lower education The mean body mass index (BMI) was 26.6 kg/m2, and was significantly correlated with systolic blood pressure. 58.9% were overweight or obese; 18.0% had raised blood pressure and 3.7% had isolated systolic hypertension. The mean number of servings of fruit consumed per day was 1.1; 33.1% had low levels of activity. Combined risk factor analysis showed that 4.1%of participants were in the low-risk group (up to 5.1% among men and 3.2% among women).Those in the high-risk group comprised 25.6% in the 25- to 44-year age group and 49.7%in the 45- to 64-year age group. Mean BMI increased by age in both sexes at least at the firstthree decades of adult life. Conclusion: Based on observed status of risk for cardiovascular health, burden of cardiovascular diseases is expected to increase if an effective prevention strategy is not undertaken

Effect of Discontinuation of Fluoride Intake from Water and Toothpaste on Urinary Excretion in Young Children

As there is no homeostatic mechanism for maintaining circulating fluoride (F) in the human body, the concentration may decrease and increase again when intake is interrupted and re-started. The present study prospectively evaluated this process in children exposed to F intake from water and toothpaste, using F in urine as a biomarker. Eleven children from Ibiá, Brazil (with sub-optimally fluoridated water supply) aged two to four years who regularly used fluoridated toothpaste (1,100 ppm F) took part in the study. Twenty-four-hour urine was collected at baseline (Day 0, F exposure from water and toothpaste) as well as after the interruption of fluoride intake from water and dentifrice (Days 1 to 28) (F interruption) and after fluoride intake from these sources had been re-established (Days 29 to 34) (F re-exposure). Urinary volume was measured, fluoride concentration was determined and the amount of fluoride excreted was calculated and expressed in mg F/day. Urinary fluoride excretion (UFE) during the periods of fluoride exposure, interruption and re-exposure was analyzed using the Wilcoxon test. Mean UFE was 0.25 mg F/day (SD: 0.15) at baseline, dropped to a mean of 0.14 mg F/day during F interruption (SD: 0.07; range: 0.11 to 0.17 mg F/day) and rose to 0.21 (SD: 0.09) and 0.19 (SD: 0.08) following F re-exposure. The difference between baseline UFE and the period of F interruption was statistically significant (p < 0.05), while the difference between baseline and the period of F re-exposure was non-significant (p > 0.05). The findings suggest that circulating F in the body of young children rapidly decreases in the first 24 hours and again increases very fast after discontinuation and re-exposure of F from water and toothpaste