Epidemioclinical Feature of Early-Onset Colorectal Cancer at-Risk for Lynch Syndrome in Central Iran

Zeinalian, Mehrdad,Hashemzadeh-Chaleshtori, Morteza,Akbarpour, Mohammad Javad,Emami, Mohammad Hassan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.11

Background: Colorectal cancer (CRC) is becoming one of the most complicated challenges of human health, particularly in developing countries like Iran. In this paper, we try to characterize CRC cases diagnosed < age 50 at-risk for Lynch syndrome within central Iran. Materials and Methods: We designed a descriptive retrospective study to screen all registered CRC patients within 2000-2013 in Poursina Hakim Research Center (PHRC), a referral gastroenterology clinic in central Iran, based on being early-onset (age at diagnosis ${\leq}50years$) and Amsterdam II criteria. We calculated frequencies and percentages by SPSS 19 software to describe clinical and family history characteristics of patients with early-onset CRC. Results: Overall 1,659 CRC patients were included in our study of which 413 (24.9%) were ${\leq}50years$ at diagnosis. Of 219/413 successful calls 67 persons (30.6%) were reported deceased. Family history was positive for 72/219 probands (32.9%) and 53 families (24.2%) were identified as familial colorectal cancer (FCC), with a history of at-least three affected members with any type of cancer in the family, of which 85% fulfilled the Amsterdam II Criteria as hereditary non-polyposis colorectal cancer (HNPCC) families (45/219 or 20.5%). Finally, 14 families were excluded due to proband tumor tissues being unavailable or unwillingness for incorporation. The most common HNPCC-associated extracolonic-cancer among both males and females of the families was stomach, at respectively 31.8 and 32.7 percent. The most common tumor locations among the 31 probands were rectum (32.3%), sigmoid (29.0%), and ascending colon (12.9%). Conclusions: Given the high prevalence of FCC (~1/4 of early-onset Iranian CRC patients), it is necessary to establish a comprehensive cancer genetic counseling and systematic screening program for early detection and to improve cancer prognosis among high risk families.

MicroRNA-183 Family in Inner Ear: Hair Cell Development and Deafness

Mohammad Reza Mahmoodian sani,Morteza Hashemzadeh Chaleshtori,Massoud Saidijam,Mohammad-Saeid Jami,Payam Ghasemi-Dehkordi 대한청각학회 2016 Journal of Audiology & Otology Vol.20 No.3

miRNAs are essential factors of an extensively conserved post-transcriptional process controlling gene expression at mRNA level. Varoius biological processes such as growth and differentiation are regulated by miRNAs. Web of Science and PubMed databases were searched using the Endnote software for the publications about the role miRNA-183 family in inner ear: hair cell development and deafness published from 2000 to 2016. A triplet of these miRNAs particularly the miR-183 family is highly expressed in vertebrate hair cells, as with some of the peripheral neurosensory cells. Point mutations in one member of this family, miR-96, underlie DFNA50 autosomal deafness in humans and lead to abnormal hair cell development and survival in mice. In zebrafish, overexpression of the miR-183 family induces extra and ectopic hair cells, while knockdown decreases the number of hair cell. The miR-183 family (miR-183, miR-96 and miR-182) is expressed abundantly in some types of sensory cell in the eye, nose and inner ear. In the inner ear, mechanosensory hair cells have a robust expression level. Despite much similarity of these miRs sequences, small differences lead to distinct targeting of messenger RNAs targets. In the near future, miRNAs are likely to be explored as potential therapeutic agents to repair or regenerate hair cells, cell reprogramming and regenerative medicine applications in animal models because they can simultaneously down-regulate dozens or even hundreds of transcripts.

Genetics of Hearing Loss in North Iran Population: An Update of Spectrum and Frequency of GJB2 Mutations

Mahbobeh Koohiyan,Fatemeh Azadegan-Dehkordi,Farideh Koohian,Morteza Hashemzadeh-Chaleshtori 대한청각학회 2019 Journal of Audiology & Otology Vol.23 No.4

Diagnosis of pre-lingual hearing loss (HL) is difficult owing to the high number of genes responsible. The most frequent cause of HL is DFNB1 due to mutations in the GJB2 gene. It represents up to 40% of HL cases in some populations. In Iran, it has previously been shown that DFNB1 accounts for 16-18% of cases but varies among different ethnic groups. Here, we reviewed results from our three previous publications and data from other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in northern Iran. In total, 903 unrelated families from six different provinces, viz., Gilan, Mazandaran, Golestan, Ghazvin, Semnan, and Tehran, were included and analyzed for the type and prevalence of GJB2 mutations. A total of 23 different genetic variants were detected from which 18 GJB2 mutations were identified. GJB2 mutations were 20.7% in the studied northern provinces, which was significantly higher than that reported in southern populations of Iran. Moreover, a gradient in the frequency of GJB2 mutations from north to south Iran was observed. c.35delG was the most common mutation, accounting for 58.4% of the cases studied. This study suggests that c.35delG mutation in GJB2 is the most important cause of HL in northern Iran.

Compound Heterozygosity for Two Novel SLC26A4 Mutations in a Large Iranian Pedigree with Pendred Syndrome

Nasrin Yazdanpanahi,Mohammad Amin Tabatabaiefar,Effat Farrokhi,Narges Abdian,Nader Bagheri,Shirin Shahbazi,Zahra Noormohammadi,Morteza Hashemzadeh Chaleshtori 대한이비인후과학회 2013 Clinical and Experimental Otorhinolaryngology Vol.6 No.4

Objectives. The aim of this study was to detect the genetic cause of deafness in a large Iranian family. Due to the importance of SLC26A4 in causing hearing loss, information about the gene mutations can be beneficial in molecular detection and management of deaf patients. Methods. We investigated the genetic etiology in a large consanguineous family with 9 deaf patients from Fars province of Iran with no GJB2 mutations. Initially, linkage analysis was performed by four DFNB4 short tandem repeat markers. The result showed linkage to DFNB4 locus. Following that, DNA sequencing of all 21 exons, their adjacent intronic sequences and the promoter of SLC26A4 was carried out for mutation detection. Results. Two novel mutations (c.863-864insT and c.881-882delAC) were identified in exon 7 of the gene, in both homozygous and compound heterozygous state in patients. Conclusion. Our results supported the importance of the SLC26A4 mutations in the etiology of hearing loss among the Iranian patients and therefore its mutation screening should be considered after GJB2 in the molecular diagnostics of hearing loss, especially when enlarged vestibular aqueduct or goiter is detected.

Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran

Fatemeh Azadegan-Dehkordi,Tayyebe Bahrami,Maryam Shirzad,Gelareh Karbasi,Nasrin Yazdanpanahi,Effat Farrokhi,Mahbobeh Koohiyan,Mohammad Amin Tabatabaiefar,Morteza Hashemzadeh-Chaleshtori 대한청각학회 2019 Journal of Audiology & Otology Vol.23 No.1

Background and Objectives: Autosomal recessive non-syndromic hearing loss (ARNSHL)with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations ingap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find thecontribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHLcases in the Kurdish population. Subjects and Methods: Genomic DNA was extractedfrom a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markerslinked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families werelinked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmationlinkage analysis (to perform a large project). Results: A total of three different mutationswere determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previouslyreported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygouspathogenic mutations of GJB2 gene was observed in nine out of the 45 families(20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observedin 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutationswas less severe than patients with c.35delG homozygous mutation (p<0.001). Conclusions:Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL inIran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in thispopulation.