Study of the association of DFNB3 locus with autosomal recessive non-syndromic hearing loss in iranian deaf population using genetic linkage analysis

Background: Hearing loss is a common sensory disorder that typically illustrates genetic heterogeneity in human populations. The incidence of congenital hearing loss is estimated at 1 in 500 births of which approximately 70 of cases are attributed to genetic factors. Genetic hearing impairment can be classified as either syndromic or non-syndromic and among non-syndromic hearing loss autosomal recessive (ALNSHL) accounts for approximately 75-80 of cases. This type of hearing loss is extremely heterogeneous and includes over 100 loci. For recessive deafness, most frequent genes are GJB2, SLC26A4, MYO15A, OTOF, and CDH23 in worldwide. This study aimed to determine the role of MYO15A (DFNB3) gene mutations in Iranian deaf population using linkage analysis. Methods: To investigate the frequency of DFNB3 gene mutation, linkage analysis was performed in 30 Iranian families with over three deaf child and negative GJB2. The negative mutations pedigrees for these gene mutations were then tested for the linkage to DFNB3 (MYO15A) locus, using short tandem repeat (STR) markers. Findings: Mutation 35delG was identified in 5 families out of 30 by sequencing the coding region of GJB2 gene. One family showed linkage to DFNB3 locus. Conclusion: Based on the results of this study, DFNB3 locus is the third cause of deafness after DFNB1 (GJB2) and DFNB4 (SLC26A4). © 2014, Isfahan University of Medical Sciences(IUMS). All rights reserved

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

Comparing the effect of cardiac biomarkers on the outcome of normotensive patients with acute pulmonary embolism

Acute pulmonary embolism (PE) is a cardiovascular challenge with potentially fatal consequences. This study was designed to observe the association of novel cardiac biomarkers with outcome in this setting. In this prospective study, from 86 patients with a confirmed diagnosis of PE, 59 patients met the inclusion criteria (22 men, 37 women; mean age, 63.36±15.04 y).The plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), tenascin-C, and D-dimer were measured at the time of confirmed diagnosis. The endpoints of the study were defined as the short-term adverse outcome and long-term all-cause mortality. Totally, 11.8% (7/59) of the patients had the short-term adverse outcome. The mean value of logNT-proBNP was 6.40±1.66 pg/ml. Among all the examined biomarkers, only the mean value of logNT-proBNP was significantly higher in the patients with the short-term adverse outcome (7.88±0.67 vs. 6.22± 1.66 pg/ml; OR, 2.359; 95% CI, 1.037 to 5.367; P=0.041). After adjustment, a threefold increase in the short-term adverse outcome was identified (OR, 3.239; 95% CI, 0.877 to 11.967; P=0.078).Overall, 18.64% (11/59) of the patients had expired by the long-term follow-up. Moreover, adjustment revealed an evidence regarding association between increased logNT-proBNP levels and long-term mortality (HR, 2.163; 95%CI, 0.910 to 5.142; P=0.081). Our study could find evidences on association between increased level of NT-proBNP and short-term adverse outcome and/or long-term mortality in PE. This biomarker may be capable of improving prediction of outcome and clinical care in non-high-risk PE