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Purpose: Hearing loss (HL) is a genetically heterogeneous common neurosensory disorder. Among different ethnic groups, pathogenic variants of Myosin XVa (MYO15A) at the DFNB3 locus are the common causes of autosomal recessive nonsyndromic hearing loss (ARNSHL). The aim of this study was to determine the prevalence and the type of MYO15A pathogenic variants in a subset of Iranian pedigrees with ARNSHL. Materials and Methods: Thirty-eight Iranian pedigrees with no Gap junction beta-2 pathogenic variants were included in the study. For all pedigrees, linkage analysis was performed using five short tandem repeat markers of DFNB3 locus. The DNA sequencing was then applied to identify MYO15A pathogenic variants in linked pedigrees. Results: Altogether, two out of 38 (5.3%) pedigrees were linked to locus 3. After sequencing, five previously unreported MYO15A pathogenic variants (c.1775-1776insA, c.1766-1767insC, c.7694delA, c.611G > C (G204A), and c.6442T > A (W2148R)) were revealed in homozygous and heterozygous state in the two pedigrees studied. Furthermore, the pathogenicity of pathogenic variants was confirmated by Insilco and cosegregation analysis in this study. Conclusions: Our findings support a relatively high prevalence and specificity of MYO15A pathogenic variant among Iranian ARNSHL patients. Molecular study of MYO15A may lead to elucidation of the population-specific pathogenic variant profile, which is of importance in molecular diagnostics of HL. [ABSTRACT FROM AUTHOR]

Background: Hearing loss (HL) is one of the most common sensory disorders (1/1000). Various studies have shown that a large proportion of autosomal recessive nonsyndromic HL (ARNSHL) in Iranian populations is caused by defects in a certain number of genes; new detection methods such as sequencing of the exome (exome-sequencing) can increase the frequency identification of responsible mutations for HL. The aim of this study was to screen for ARNSHL pedigrees and to find the responsible genes. Materials and Methods: Fifty big ARNSHL pedigrees including 130 Iranian patients with ARNSHL took part in this study. Direct sequencing and multiplex polymerase chain reaction were, respectively, used for the presence of GJB2 and GJB6 (del D13S1830 and del D13S1854) mutations in all of the families. The negative pedigrees for these genes were tested to homozygosity mapping for the linkage to nine known loci, then the negative pedigrees for them were sent for exome-sequencing. Results: Nine of 50 pedigrees had GJB2 (18%) mutations. No GJB6 mutation was found. Totally, 11 of 50 pedigrees (22%) showed linkage to 6 known loci DFNB, including 2 pedigrees to DFNB2, 2 pedigrees to DFNB3, 2 pedigrees to DFNB4, 2 pedigrees to DFNB7/11, 3 pedigrees to DFNB12, and 2 pedigrees to DFNB104. An individual from a large pedigree was examined by exome-sequencing and was observed no changes. Conclusion: In this study, DFNB1 and DFNB12 are the main causes of ARNSHL. GJB6 mutations, DFNB6, and DFNB59 were absent. Therefore, 40% of the ARNSHL etiology was found in this study. [ABSTRACT FROM AUTHOR]

Background: Microsatellite instability (MSI) is a mutational signature that is the hallmark of Lynch syndrome, and MSI testing is a cost-effective method to screen the disease. Since there is no enough data about MSI status and associated clinicopathologic features of hereditary nonpolyposis colorectal cancer (HNPCC) in Iran, our study is a new trial to describe them in center of Iran (Isfahan). Materials and Methods: It is a descriptive retrospective study to screen HNPCC families using Amsterdam II criteria in Central Iran within 2000-2013. For MSI testing, we used a commercially available kit evaluating mononucleotide markers (BAT-25, BAT-26, MON0-27, NR-21 and NR-24). After a fluorescent multiplex polymerase chain reaction amplification of the markers, samples were sequenced to fragment analysis. Data analysis was performed using SPSS 16 software (SPSS Inc., Chicago, IL, USA). Results: Overall, 31 of 45 screened HNPCC families were eventually included to MSI testing. Totally, 9/31 patients (29.0%) showed MSI in their tumor tissues. BAT-26 was the most instable marker with instability in 7/24 MSI tumors (29.2%). The mean age at diagnosis in microsatellite stable (MSS), MSI-Low (MSI-L), and MSI-High (MSI-H) probands was respectively 44.7 (standard deviation [SD] = 11.83), 51.7 (SD = 16.17), and 36.0 (SD = 3.41) years. The most common tumor sites in MSS, MSI-L, and MSI-H probands were rectosigmoid (~72.8%), rectum (66.7%) and right colon (50.0%), respectively. Of 186 cancer patients among 31 HNPCC families, 86 patients (46.2%) had colorectal cancer (CRC) and 100 patients (53.8%) had extracolonic cancers. The average of CRC affected members among MSS, MSI-L, and MSI-H groups of our HNPCC families was 2.2 (SD = 1.30), 3.3 (SD = 3.21), and 4.7 (SD = 2.42) patients per family, respectively. Stomach with 18.3% and 26.7% of all extracolonic cancers were most common involved organ in MSS and MSI-H families, respectively. Conclusion: Our different molecular results could be suggested to describe HNPCC families based on some new molecular mechanisms leading to MSS HNPCC phenotypes. Meanwhile, more evaluations within our population are recommended. [ABSTRACT FROM AUTHOR]