Niloofar Bazazzadegan

Publications (11)17.67 Total impact

• Article: A comprehensive study to determine heterogeneity of autosomal recessive nonsyndromic hearing loss in Iran.

  Mojgan Babanejad, Zohreh Fattahi, Niloofar Bazazzadegan, Carla Nishimura, Nicole Meyer, Nooshin Nikzat, Elahe Sohrabi, Amin Najmabadi, Peyman Jamali, Farkhonde Habibi, Richard J H Smith, Kimia Kahrizi, Hossein Najmabadi
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  ABSTRACT: Hearing loss is the most common sensory disorder worldwide and affects 1 of every 500 newborns. In developed countries, at least 50% of cases are genetic, most often resulting in nonsyndromic deafness (70%), which is usually autosomal recessive (∼80%). Although the cause of hearing loss is heterogeneous, mutations in GJB2 gene at DFNB1 locus are the major cause of autosomal recessive nonsyndromic hearing loss (ARNSHL) in many populations. Our previous study showed that mutations of GJB2 gene do not contribute to the major genetic load of deafness in the Iranian population (∼16%). Therefore, to define the importance of other genes in contributing to an ARNSHL phenotype in the Iranian population, we used homozygosity mapping to identify regions of autozygosity-by-descent in 144 families which two or more progeny had ARNSHL but were negative for GJB2 gene mutations. Using flanking or intragenic short-tandem repeat markers for 33 loci we identified 33 different homozygous variations in 10 genes, of which 9 are novel. In aggregate, these data explain ∼40% of genetic background of ARNHSL in the Iranian population. © 2012 Wiley Periodicals, Inc.
  American Journal of Medical Genetics Part A 08/2012; 158A(10):2485-92. · 2.39 Impact Factor
• Source

  Available from: Eliot Shearer

  Article: Screening for MYO15A gene mutations in autosomal recessive nonsyndromic, GJB2 negative Iranian deaf population.

  Zohreh Fattahi, A Eliot Shearer, Mojgan Babanejad, Niloofar Bazazzadegan, Seyed Navid Almadani, Nooshin Nikzat, Khadijeh Jalalvand, Sanaz Arzhangi, Fatemehsadat Esteghamat, Rezvan Abtahi, Batool Azadeh, Richard J H Smith, Kimia Kahrizi, Hossein Najmabadi
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  ABSTRACT: MYO15A is located at the DFNB3 locus on chromosome 17p11.2, and encodes myosin-XV, an unconventional myosin critical for the formation of stereocilia in hair cells of cochlea. Recessive mutations in this gene lead to profound autosomal recessive nonsyndromic hearing loss (ARNSHL) in humans and the shaker2 (sh2) phenotype in mice. Here, we performed a study on 140 Iranian families in order to determine mutations causing ARNSHL. The families, who were negative for mutations in GJB2, were subjected to linkage analysis. Eight of these families showed linkage to the DFNB3 locus, suggesting a MYO15A mutation frequency of 5.71% in our cohort of Iranian population. Subsequent sequencing of the MYO15A gene led to identification of 7 previously unreported mutations, including 4 missense mutations, 1 nonsense mutation, and 2 deletions in different regions of the myosin-XV protein.
  American Journal of Medical Genetics Part A 06/2012; 158A(8):1857-64. · 2.39 Impact Factor
• Article: The spectrum of GJB2 mutations in the Iranian population with non-syndromic hearing loss-A twelve year study.

  Niloofar Bazazzadegan, Nooshin Nikzat, Zohreh Fattahi, Carla Nishimura, Nicole Meyer, Shima Sahraian, Payman Jamali, Mojgan Babanejad, Atie Kashef, Hilda Yazdan, [......], Maryam Taghdiri, Batool Azadeh, Faezeh Mojahedi, Atefeh Khoshaeen, Haleh Habibi, Farahnaz Reyhanifar, Narges Nouri, Richard J H Smith, Kimia Kahrizi, Hossein Najmabadi
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  ABSTRACT: Mutations in GJB2, encoding connexin 26 (CX26), are causally related to autosomal recessive form of non-syndromic hearing loss (NSHL) at the DFNB1 locus and autosomal dominant NSHL at the DFNA3 locus. In this study, we investigated the prevalence of GJB2 mutations in the Iranian deaf population. A total of 2322 deaf probands presenting the ethnically diverse Iranian population were screened for variants in GJB2. All persons were first screened for the c.35delG mutation, as this variant is the most prevalent GJB2-deafness causing mutation in the Iranian population. In all persons carrying zero or one c.35delG allele, exons 1 and 2 were then sequenced. In total, 374 (∼16%) families segregated GJB2-related deafness caused by 45 different mutations and 5 novel variants. The c.35delG mutation was most commonly identified and accounts for ∼65% of the GJB2 mutations found in population studied. Our data also show that there is a gradual decrease in the frequency of the c.35delG mutation and of GJB2-related deafness in general in a cline across Iran extending from the northwest to southeast.
  International journal of pediatric otorhinolaryngology 06/2012; 76(8):1164-74. · 0.85 Impact Factor
• Article: Spectrum of GJB2 (Cx26) gene mutations in Iranian Azeri patients with nonsyndromic autosomal recessive hearing loss.

  Behzad Davarnia, Mojgan Babanejad, Zohreh Fattahi, Nooshin Nikzat, Niloofar Bazazzadegan, Akbar Pirzade, Reza Farajollahi, Carla Nishimura, Khadijeh Jalalvand, Sanaz Arzhangi, Kimia Kahrizi, Richard J H Smith, Hossein Najmabadi
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  ABSTRACT: Hereditary hearing impairment is a genetically heterogeneous disorder. In spite of this, mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of nonsyndromic recessive hearing loss in many countries and are largely dependent on ethnic groups. The purpose of our study was to characterize the type and prevalence of GJB2 mutations among Azeri population of Iran. Fifty families presenting autosomal recessive nonsyndromic hearing loss from Ardabil province of Iran were studied for mutations in GJB2 gene. All DNA samples were screened for c.35delG mutation by ARMS PCR. Samples from patients who were normal for c.35delG were analyzed for the other variations in GJB2 by direct sequencing. In the absence of mutation detection, GJB6 was screened for the del(GJB6-D13S1830) and del(GJB6-D13S1854). Thirteen families demonstrated alteration in the Cx26 (26%). The 35delG mutation was the most common one, accounting for 69.2% (9 out of 13 families). All the detected families were homozygous for this mutation. Two families were homozygous for delE120 and 299-300delAT mutations. We also identified a novel mutation: c.463-464 delTA in 2 families resulting in a frame shift mutation. Our results suggest that c.35delG mutation in the GJB2 gene is the most important cause of GJB2 related deafness in Iranian Azeri population.
  International journal of pediatric otorhinolaryngology 12/2011; 76(2):268-71. · 0.85 Impact Factor
• Article: Did the GJB2 35delG mutation originate in Iran?

  Vahideh Norouzi, Hiva Azizi, Zohreh Fattahi, Fatemehsadat Esteghamat, Niloofar Bazazzadegan, Carla Nishimura, Nooshin Nikzat, Khadijeh Jalalvand, Kimia Kahrizi, Richard J H Smith, Hossein Najmabadi
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  ABSTRACT: Mutations in GJB2 are a major cause of autosomal recessive non-syndromic hearing loss (ARNSHL) in many populations. A single mutation of this gene (35delG) accounts for approximately 70% of GJB2 mutations that are associated with ARNSHL in Caucasians in many European countries and also in Iranian. In this study, we used PCR and restriction digestion to genotype five single nucleotide polymorphisms (SNPs) that define the genetic background of the 35delG mutation over an interval of 98 Kbp that includes the coding and flanking regions of GJB2. Two microsatellite markers, D13S175 and D13S141, were also analyzed in patients and controls. These data suggest that the 35delG mutation originated in northern Iran.
  American Journal of Medical Genetics Part A 09/2011; 155A(10):2453-8. · 2.39 Impact Factor
• Article: Two Iranian families with a novel mutation in GJB2 causing autosomal dominant nonsyndromic hearing loss.

  Niloofar Bazazzadegan, Abraham M Sheffield, Masoomeh Sobhani, Kimia Kahrizi, Nicole C Meyer, Guy Van Camp, Nele Hilgert, Seyedeh Sedigheh Abedini, Farkhondeh Habibi, Ahmad Daneshi, Carla Nishimura, Matthew R Avenarius, Mohammad Farhadi, Richard J H Smith, Hossein Najmabadi
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  ABSTRACT: Mutations in GJB2, encoding connexin 26 (Cx26), cause both autosomal dominant and autosomal recessive nonsyndromic hearing loss (ARNSHL) at the DFNA3 and DFNB1 loci, respectively. Most of the over 100 described GJB2 mutations cause ARNSHL. Only a minority has been associated with autosomal dominant hearing loss. In this study, we present two families with autosomal dominant nonsyndromic hearing loss caused by a novel mutation in GJB2 (p.Asp46Asn). Both families were ascertained from the same village in northern Iran consistent with a founder effect. This finding implicates the D46N missense mutation in Cx26 as a common cause of deafness in this part of Iran mandating mutation screening of GJB2 for D46N in all persons with hearing loss who originate from this geographic region.
  American Journal of Medical Genetics Part A 05/2011; 155A(5):1202-11. · 2.39 Impact Factor
• Source

  Available from: Mahdi Malekpour

  Article: Clinical Application of Screening for GJB2 Mutations before Cochlear Implantation in a Heterogeneous Population with High Rate of Autosomal Recessive Nonsyndromic Hearing Loss.

  Masoud Motasaddi Zarandy, Mersedeh Rohanizadegan, Hojjat Salmasian, Nooshin Nikzad, Niloofar Bazazzadegan, Mahdi Malekpour
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  ABSTRACT: Clinical application of mutation screening and its effect on the outcome of cochlear implantation is widely debated. We investigated the effect of mutations in GJB2 gene on the outcome of cochlear implantation in a population with a high rate of consanguineous marriage and autosomal recessive nonsyndromic hearing loss. Two hundred and one children with profound prelingual sensorineural hearing loss were included. Forty-six patients had 35delG in GJB2. Speech awareness thresholds (SATs) and speech recognition thresholds (SRTs) improved following implantation, but there was no difference in performance between patients with GJB2-related deafness versus control (all P > 0.10). Both groups had produced their first comprehensible words within the same period of time following implantation (2.27 months in GJB2-related deaf versus 2.62 months in controls, P = 0.22). Although our findings demonstrate the need to uncover unidentified genetic causes of hereditary deafness, they do not support the current policy for genetic screening before cochlear implantation, nor prove a prognostic value.
  Genetics research international. 01/2011; 2011:787026.
• Source

  Available from: Eliot Shearer

  Article: Mutations in TMC1 are a common cause of DFNB7/11 hearing loss in the Iranian population.

  Michael S Hildebrand, Kimia Kahrizi, Catherine J Bromhead, A Eliot Shearer, Jennifer A Webster, Hossein Khodaei, Rezvan Abtahi, Niloofar Bazazzadegan, Mojgan Babanejad, Nooshin Nikzat, William J Kimberling, Dietrich Stephan, Patrick L M Huygen, Melanie Bahlo, Richard J H Smith, Hossein Najmabadi
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  ABSTRACT: We investigated the cause of autosomal recessive nonsyndromic hearing loss (ARNSHL) that segregated in 2 consanguineous Iranian families. Otologic and audiometric examinations were performed on affected members of each family. Genome-wide parametric multipoint linkage mapping using a recessive model was performed with Affymetrix 50K GeneChips or short tandem repeat polymorphisms. Direct sequencing was used to confirm the causative mutation in each family. In 2 Iranian families, L-1651 and L-8600606, with ARNSHL that mapped to the DFNB7/11 locus, homozygosity for a reported splice site mutation (c.776+1G>A), and a novel deletion (c.1589_1590delCT; p.S530*) were identified in the TMC1 gene, respectively. Consistent with the previously reported phenotype in DFNB7/11 families, the 2 Iranian families had segregated congenital, profound hearing impairment. However, in family L-1651, one affected family member (IV:3) has milder hearing impairment than expected, suggesting a potential genetic modifier effect. These results indicate that DFNB7/11 is a common form of genetic hearing loss in Iran, because this population is the source of 6 of the 29 TMC1 mutations reported worldwide.
  The Annals of otology, rhinology, and laryngology 12/2010; 119(12):830-5. · 1.05 Impact Factor
• Article: Identification of SLC26A4 gene mutations in Iranian families with hereditary hearing impairment.

  Kimia Kahrizi, Marzieh Mohseni, Carla Nishimura, Niloofar Bazazzadegan, Stephanie M Fischer, Atefeh Dehghani, Morteza Sayfati, Maryam Taghdiri, Payman Jamali, Richard J H Smith, Fereydoun Azizi, Hossein Najmabadi
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  ABSTRACT: Mutations in the SLC26A4 gene at the DFNB4 locus are responsible for Pendred syndrome and non-syndromic hereditary hearing loss (DFNB4). This study included 80 nuclear families with two or more siblings segregating presumed autosomal recessive hearing loss. All deaf persons tested negative for mutations in GJB2 at the DFNB1 locus and were, therefore, screened for autozygosity by descent (ABD) using short tandem repeat polymorphisms (STRPs) that flanked SLC26A4. In 12 families, homozygosity for STRPs suggested possible ABD in this genomic region. Affected individuals in five families had a positive perchlorate discharge test. Sequence analysis of SLC26A4 identified ten mutations in eight families (T420I, 1197delT, G334V, R409H, T721M, R79X, S448L, L597S, 965insA and L445W), of which, four are novel (T420I, G334V, 965insA and R79X). These results imply that Pendred syndrome is the most prevalent form of syndromic hereditary hearing loss in Iran.
  European Journal of Pediatrics 10/2008; 168(6):651-3. · 1.88 Impact Factor
• Source

  Available from: ias.ac.in

  Article: GJB2 mutations in Baluchi population.

  Anoosh Naghavi, Carla Nishimura, Kimia Kahrizi, Yasser Riazalhosseini, Niloofar Bazazzadegan, Marzieh Mohseni, Richard J H Smith, Hossein Najmabadi
  Journal of Genetics 09/2008; 87(2):195-7. · 1.09 Impact Factor
• Article: GJB2 mutations: passage through Iran.

  Hossein Najmabadi, Carla Nishimura, Kimia Kahrizi, Yasser Riazalhosseini, Mahdi Malekpour, Ahmad Daneshi, Mohammad Farhadi, Marzieh Mohseni, Nejat Mahdieh, Ahmad Ebrahimi, Niloofar Bazazzadegan, Anoosh Naghavi, Matthew Avenarius, Sanaz Arzhangi, Richard J H Smith
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  ABSTRACT: Hereditary hearing loss (HHL) is a very common disorder. When inherited in an autosomal recessive manner, it typically presents as an isolated finding. Interestingly and unexpectedly, in spite of extreme heterogeneity, mutations in one gene, GJB2, are the most common cause of congenital severe-to-profound deafness in many different populations. In this study, we assessed the contributions made by GJB2 mutations and chromosome 13 g.1777179_2085947del (the deletion more commonly known as del (GJB6-D13S1830) that includes a portion of GJB6 and is hereafter called Delta(GJB6-D13S1830)) to the autosomal recessive non-syndromic deafness (ARNSD) genetic load in Iran. Probands from 664 different nuclear families were investigated. GJB2-related deafness was found in 111 families (16.7%). The carrier frequency of the 35delG mutation showed a geographic variation that is supported by studies in neighboring countries. Delta(GJB6-D13S1830) was not found. Our prevalence data for GJB2-related deafness reveal a geographic pattern that mirrors the south-to-north European gradient and supports a founder effect in southeastern Europe.
  American Journal of Medical Genetics Part A 04/2005; 133A(2):132-7. · 2.39 Impact Factor