Marzieh Mohseni
@uswr.ac.ir
Genetic Research Center
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences
Research Assistant Professor,
Genetics Research Center, USWR
Tehran, Iran.
EDUCATION
PhD of Medical Genetics,
RESEARCH INTERESTS
Genetic,Hearing Loss, NGS
Scopus Publications
Scopus Publications
Somayeh Alinaghi, Marzieh Mohseni, Zohreh Fattahi, Maryam Beheshtian, Fatemeh Ghodratpour, Farzane Zare Ashrafi, Sanaz Arzhangi, Khadijeh Jalalvand, Reza Najafipour, Hamid Reza Khorram Khorshid,et al.
Maad Rayan Publishing Company
Background: The study of Y-chromosomal variations provides valuable insights into male susceptibility in certain diseases like cardiovascular disease (CVD). In this study, we analyzed paternal lineage in different Iranian ethnic groups, not only to identify developing medical etiology, but also to pave the way for gender-specific targeted strategies and personalized medicine in medical genetic research studies. Methods: The diversity of eleven Iranian ethnic groups was studied using 27 Y-chromosomal short tandem repeat (Y-STR) haplotypes from Y-filer® Plus kit. Analysis of molecular variance (AMOVA) based on pair-wise RST along with multidimensional scaling (MDS) calculation and Network phylogenic analysis was employed to quantify the differences between 503 unrelated individuals from each ethnicity. Results: Results from AMOVA calculation confirmed that Gilaks and Azeris showed the largest genetic distance (RST=0.35434); however, Sistanis and Lurs had the smallest considerable genetic distance (RST=0.00483) compared to other ethnicities. Although Azeris had a considerable distance from other ethnicities, they were still close to Turkmens. MDS analysis of ethnic groups gave the indication of lack of similarity between different ethnicities. Besides, network phylogenic analysis demonstrated insignificant clustering between samples. Conclusion: The AMOVA analysis results explain that the close distance of Azeris and Turkmens may be the effect of male-dominant expansions across Central Asia that contributed to historical and demographics of populations in the region. Insignificant differences in network analysis could be the consequence of high mutation events that happened in the Y-STR regions over the years. Considering the ethnic group affiliations in medical research, our results provided an understanding and characterization of Iranian male population for future medical and population genetics studies.
Sepideh Mehvari, Nahid Karimian Fathi, Sara Saki, Maryam Asadnezhad, Sanaz Arzhangi, Fatemeh Ghodratpour, Marzieh Mohseni, Farzane Zare Ashrafi, Saeed Sadeghian, Mohammadali Boroumand,et al.
Wiley
AbstractCoronary artery disease (CAD), the most prevalent cardiovascular disease, is the leading cause of death worldwide. Heritable factors play a significant role in the pathogenesis of CAD. It has been proposed that approximately one‐third of patients with CAD have a positive family history, and individuals with such history are at ~1.5‐fold increased risk of CAD in their lifespans. Accordingly, the long‐recognized familial clustering of CAD is a strong risk factor for this disease. Our study aimed to identify candidate genetic variants contributing to CAD by studying a cohort of 60 large Iranian families with at least two members in different generations afflicted with premature CAD (PCAD), defined as established disease at ≤45 years in men and ≤55 years in women. Exome sequencing was performed for a subset of the affected individuals, followed by prioritization and Sanger sequencing of candidate variants in all available family members. Subsequently, apparently healthy carriers of potential risk variants underwent coronary computed tomography angiography (CCTA), followed by co‐segregation analysis of the combined data. Putative causal variants were identified in seven genes, ABCG8, CD36, CYP27A1, PIK3C2G, RASSF9, RYR2, and ZFYVE21, co‐segregating with familial PCAD in seven unrelated families. Among these, PIK3C2G, RASSF9, and ZFYVE21 are novel candidate CAD susceptibility genes. Our findings indicate that rare variants in genes identified in this study are involved in CAD development.
Fereshteh Jamshidi, Ebrahim Shokouhian, Marzieh Mohseni, Kimia Kahrizi, Hossein Najmabadi, and Mojgan Babanejad
Wiley
BACKGROUND
To date, over 400 syndromes with hearing impairment have been identified which altogether constitute almost 30% of hereditary hearing loss (HL) cases around the globe. Manifested as complete or partial labyrinthine aplasia (severe malformations of the inner ear structure), type I microtia (smaller outer ear with shortened auricles), and microdontia (small and widely spaced teeth), labyrinthine aplasia, microtia, and microdontia (LAMM) syndrome (OMIM 610706) is an extremely rare autosomal recessive condition caused by bi-allelic mutations in the FGF3 gene.
METHODS
Using the whole-exome sequencing (WES) data of the proband, we analyzed a consanguineous Iranian family with three affected members presenting with congenital bilateral HL, type I microtia, and microdontia.
RESULTS
We discovered the homozygous deletion c.45delC in the first exon of the FGF3 gene, overlapping a 38.72 Mb homozygosity region in chromosome 11. Further investigations using Sanger sequencing revealed that this variant co-segregated with the phenotype observed in the family.
CONCLUSION
Here, we report the first identified case of LAMM syndrome in Iran, and by identifying a frameshift variant in the first exon of the FGF3 gene, our result will help better clarify the phenotype-genotype relation of LAMM syndrome.
Marzieh Mohseni, Yusuf Mohammadi, Farzane Zare Ashrafi, Fatemeh Ghodratpour, Khadijeh Jalalvand, Sanaz Arzhangi, Mojgan Babanejad, Mohammad Hossein Azizi, Kimia Kahrizi, and Hossein Najmabadi
Maad Rayan Publishing Company
Genetic analysis of non-syndromic hearing loss (NSHL) has been challenged due to marked clinical and genetic heterogeneity. Today, advanced next-generation sequencing (NGS) technologies, such as exome sequencing (ES), have drastically increased the efficacy of gene identification in heterogeneous Mendelian disorders. Here, we present the utility of ES and re-evaluate the phenotypic data for identifying candidate causal variants for previously unexplained progressive moderate to severe NSHL in an extended Iranian family. Using this method, we identified a known heterozygous nonsense variant in exon 26 of the DIAPH1 gene (MIM: 602121), which led to "Deafness, autosomal dominant 1, with or without thrombocytopenia; DFNA1" (MIM: 124900) in this large family in the absence of GJB2 disease-causing variants and also OtoSCOPE-negative results. To the best of our knowledge, this nonsense variant (NM_001079812.3):c.3610C>T (p.Arg1204Ter) is the first report of the DIAPH1 gene variant for autosomal dominant non-syndromic hearing loss (ADNSHL) in Iran.
Farzane Zare Ashrafi, Marzieh Mohseni, Maryam Beheshtian, Zohreh Fattahi, Fatemeh Ghodratpour, Fatemeh Keshavarzi, Hanieh Behravan, Marzieh Kalhor, Khadijeh Jalalvand, Maryam Azad,et al.
Maad Rayan Publishing Company
Background: Global real-time monitoring of SARS-CoV-2 variants is crucial to controlling the COVID-19 outbreak. The purpose of this study was to set up a Sanger-based platform for massive SARS-CoV-2 variant tracking in laboratories in low-resource settings. Methods: We used nested RT-PCR assay, Sanger sequencing and lineage assignment for 930-bp of the SARS-CoV-2 spike gene, which harbors specific variants of concern (VOCs) mutations. We set up our platform by comparing its results with whole genome sequencing (WGS) data on 137 SARS-CoV-2 positive samples. Then, we applied it on 1028 samples from March-September 2021. Results: In total, 125 out of 137 samples showed 91.24% concordance in mutation detection. In lineage assignment, 123 out of 137 samples demonstrated 89.78% concordance, 65 of which were assigned as VOCs and showed 100% concordance. Of 1028 samples screened by our in-house method, 78 distinct mutations were detected. The most common mutations were: S:D614G (21.91%), S:P681R (12.19%), S:L452R (12.15%), S:T478K (12.15%), S:N501Y (8.91%), S:A570D (8.89%), S:P681H (8.89%), S:T716I (8.74%), S:L699I (3.50%) and S:S477N (0.28%). Of 1028 samples, 980 were attributed as VOCs, which include the Delta (B.1.617.2) and Alpha (B.1.1.7) variants. Conclusion: Our proposed in-house Sanger-based assay for SARS-CoV-2 lineage assignment is an accessible strategy in countries with poor infrastructure facilities. It can be applied in the rapid tracking of SARS-CoV-2 VOCs in the SARS-CoV-2 pandemic.
Maryam Hosseinpour, Fariba Ardalani, Marzieh Mohseni, Maryam Beheshtian, Sanaz Arzhangi, Shahrzad Ossareh, Hossein Najmabadi, Ali Nobakht, Kimia Kahrizi, and Behrooz Broumand
Maad Rayan Publishing Company
Background: Autosomal dominant polycystic kidney disease (ADPKD), one of the common inherited disorders in humans, is characterized by the development and enlargement of renal cysts, often leading to end-stage renal disease (ESRD). In this study, Iranian ADPKD families were subjected to high-throughput DNA sequencing to find potential causative variants facilitating the way toward risk assessment and targeted therapy. Methods: Our protocol was based on the targeted next generation sequencing (NGS) panel previously developed in our center comprising 12 genes involved in PKD. This panel has been applied to investigate the genetic causes of 32 patients with a clinical suspicion of ADPKD. Results: We identified a total of 31 variants for 32 individuals, two of which were each detected in two individuals. Twenty-seven out of 31 detected variants were interpreted as pathogenic/likely pathogenic and the remaining 4 of uncertain significance with a molecular diagnostic success rate of 87.5%. Among these variants, 25 PKD1/2 pathogenic/likely pathogenic variants were detected in 32 index patients (78.1%), and variants of uncertain significance in four individuals (12.5% in PKD1/2). The majority of variants was identified in PKD1 (74.2%). Autosomal recessive PKD was identified in one patient, indicating the similarities between recessive and dominant PKD. In concordance with earlier studies, this biallelic PKD1 variant, p.Arg3277Cys, leads to rapidly progressive and severe disease with very early-onset ADPKD. Conclusion: Our findings suggest that targeted gene panel sequencing is expected to be the method of choice to improve diagnostic and prognostic accuracy in PKD patients with heterogeneity in genetic background.
Zohreh Fattahi, Marzieh Mohseni, Maryam Beheshtian, Ali Jafarpour, Khadijeh Jalalvand, Fatemeh Keshavarzi, Hanieh Behravan, Fatemeh Ghodratpour, Farzane Zare Ashrafi, Marzieh Kalhor,et al.
Maad Rayan Publishing Company
Background: Complete SARS-CoV-2 genome sequencing in the early phase of the outbreak in Iran showed two independent viral entries. Subsequently, as part of a genome surveillance project, we aimed to characterize the genetic diversity of SARS-CoV-2 in Iran over one year after emerging. Methods: We provided 319 SARS-CoV-2 whole-genome sequences used to monitor circulating lineages in March 2020-May 2021 time interval. Results: The temporal dynamics of major SARS-CoV-2 clades/lineages circulating in Iran is comparable to the global perspective and represent the 19A clade (B.4) dominating the first disease wave, followed by 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7), leading the second, third and fourth waves, respectively. We observed a mixture of circulating B.1.36, B.1.1.413, B.1.1.7 lineages in winter 2021, paralleled in a fading manner for B.1.36/B.1.1.413 and a growing rise for B.1.1.7, prompting the fourth outbreak. Entry of the Delta variant, leading to the fifth disease wave in summer 2021, was detected in April 2021. This study highlights three lineages as hallmarks of the SARS-CoV-2 outbreak in Iran; B4, dominating early periods of the epidemic, B.1.1.413 (B.1.1 with the combination of [D138Y-S477N-D614G] spike mutations) as a characterizing lineage in Iran, and the co-occurrence of [I100T-L699I] spike mutations in half of B.1.1.7 sequences mediating the fourth peak. It also designates the renowned combination of G and GR clades’ mutations as the top recurrent mutations. Conclusion: In brief, we provided a real-time and comprehensive picture of the SARS-CoV-2 genetic diversity in Iran and shed light on the SARS-CoV-2 transmission and circulation on the regional scale.
Zohreh Fattahi, Marzieh Mohseni, Khadijeh Jalalvand, Fatemeh Aghakhani Moghadam, Azam Ghaziasadi, Fatemeh Keshavarzi, Jila Yavarian, Ali Jafarpour, Seyedeh Elham Mortazavi, Fatemeh Ghodratpour,et al.
Hindawi Limited
Abstract The SARS‐CoV‐2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence. While Iran was among the first countries confronted with rapid spread of virus in February 2020, no real‐time SARS‐CoV‐2 whole‐genome tracking in early phase of outbreak was performed in the country. To address this issue, we provided 50 whole‐genome sequences of viral isolates ascertained from different geographical locations in Iran during March–July 2020. The corresponding analysis on origins, transmission dynamics and genetic diversity of SARS‐CoV‐2 virus, represented at least two introductions of the virus into the country, constructing two major clusters defined as B.4 and B.1*. The first entry of the virus might have occurred around very late 2019/early 2020, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission that led to dominancy of B.4 lineage in early epidemic till the end of June. Gradually, reduction in dominancy of B.4 occurred possibly as a result of other entries of the virus, followed by surge of B.1* lineages, as of mid‐May. Remarkably, variation tracking of the virus indicated the increase in frequency of D614G mutation, along with B.1* lineages, which showed continuity till October 2020. The increase in frequency of D614G mutation and B.1* lineages from mid‐May onwards predicts a rapid viral transmission that may push the country into a critical health situation followed by a considerable change in composition of viral lineages circulating in the country.
Mojgan Babanejad, Maryam Beheshtian, Fereshteh Jamshidi, Marzieh Mohseni, Kevin T. Booth, Kimia Kahrizi, and Hossein Najmabadi
Springer Science and Business Media LLC
Marzieh Mohseni, Mojgan Babanejad, Kevin T. Booth, Payman Jamali, Khadijeh Jalalvand, Behzad Davarnia, Fariba Ardalani, Atefeh Khoshaeen, Sanaz Arzhangi, Fatemeh Ghodratpour,et al.
Wiley
Hearing loss (HL) is one of the most common sensory defects affecting more than 466 million individuals worldwide. It is clinically and genetically heterogeneous with over 120 genes causing non‐syndromic HL identified to date. Here, we performed exome sequencing (ES) on a cohort of Iranian families with no disease‐causing variants in known deafness‐associated genes after screening with a targeted gene panel. We identified likely causal variants in 20 out of 71 families screened. Fifteen families segregated variants in known deafness‐associated genes. Eight families segregated variants in novel candidate genes for HL: DBH, TOP3A, COX18, USP31, TCF19, SCP2, TENM1, and CARMIL1. In the three of these families, intrafamilial locus heterogeneity was observed with variants in both known and novel candidate genes. In aggregate, we were able to identify the underlying genetic cause of HL in nearly 30% of our study cohort using ES. This study corroborates the observation that high‐throughput DNA sequencing in populations with high rates of consanguineous marriages represents a more appropriate strategy to elucidate the genetic etiology of heterogeneous conditions such as HL.
Maryam Beheshtian, Tara Akhtarkhavari, Sepideh Mehvari, Marzieh Mohseni, Zohreh Fattahi, Seyedeh Sedigheh Abedini, Sanaz Arzhangi, Mahsa Fadaee, Payman Jamali, Reza Najafipour,et al.
Wiley
Mutations in adaptor protein complex‐4 (AP‐4) genes have first been identified in 2009, causing a phenotype termed as AP‐4 deficiency syndrome. Since then several patients with overlapping phenotypes, comprised of intellectual disability (ID) and spastic tetraplegia have been reported. To delineate the genotype‐phenotype correlation of the AP‐4 deficiency syndrome, we add the data from 30 affected individuals from 12 out of 640 Iranian families with ID in whom we detected disease‐causing variants in AP‐4 complex subunits, using next‐generation sequencing. Furthermore, by comparing genotype‐phenotype findings of those affected individuals with previously reported patients, we further refine the genotype‐phenotype correlation in this syndrome. The most frequent reported clinical findings in the 101 cases consist of ID and/or global developmental delay (97%), speech disorders (92.1%), inability to walk (90.1%), spasticity (77.2%), and microcephaly (75.2%). Spastic tetraplegia has been reported in 72.3% of the investigated patients. The major brain imaging findings are abnormal corpus callosum morphology (63.4%) followed by ventriculomegaly (44.5%). Our result might suggest the AP‐4 deficiency syndrome as a major differential diagnostic for unknown hereditary neurodegenerative disorders.
Goli Kazemi, Fatemeh Peymani, Marzieh Mohseni, Farzane Zare Ashrafi, Sanaz Arzhangi, Fariba Ardalani, Fatemeh Aghakhani Moghaddam, Kimia Kahrizi, and Hossein Najmabadi
Maad Rayan Publishing Company
Background: Recently, we have reported mutations in LARP7 gene, leading to neurodevelopmental disorders (NDDs), the most frequent cause of disability in children with a broad phenotype spectrum and diverse genetic landscape. Methods: Here, we present two Iranian patients from consanguineous families with syndromic intellectual disability, facial dysmorphism, and short stature. Results: Whole-exome sequencing (WES) revealed a novel homozygous stop-gain (c.C925T, p.R309X) variant and a previously known homozygous acceptor splice-site (c.1669-1_1671del) variant in LARP7 gene, indicating the diagnosis of Alazami syndrome. Conclusion: These identified variants in patients with Alazami syndrome were consistent with previously reported loss of function variants in LARP7 and provide further evidence that loss of function of LARP7 is the disease mechanism.
Sara Taghizadeh, Raheleh Vazehan, Maryam Beheshtian, Farnaz Sadeghinia, Zohreh Fattahi, Marzieh Mohseni, Sanaz Arzhangi, Shahriar Nafissi, Ariana Kariminejad, Hossein Najmabadi,et al.
Maad Rayan Publishing Company
Background: Inherited peripheral neuropathies (IPNs) are a group of neuropathies affecting peripheral motor and sensory neurons. Charcot-Marie-Tooth (CMT) disease is the most common disease in this group. With recent advances in next-generation sequencing (NGS) technologies, more than 100 genes have been implicated for different types of CMT and other clinically and genetically inherited neuropathies. There are also a number of genes where neuropathy is a major feature of the disease such as spinocerebellar ataxia (SCA) and hereditary spastic paraplegia (HSP). We aimed to determine the genetic causes underlying IPNs in Iranian families. Methods: We performed whole exome sequencing (WES) for 58 PMP22 deletion-/duplication-negative unrelated Iranian patients with a spectrum of phenotypes and with a preliminary diagnosis of hereditary neuropathies. Results: Twenty-seven (46.6%) of the cases were genetically diagnosed with pathogenic or likely pathogenic variants. In this study, we identified genetically strong variants within genes not previously linked to any established disease phenotype in five (8.6%) patients. Conclusion: Our results highlight the advantage of using WES for genetic diagnosis in highly heterogeneous diseases such as IPNs. Moreover, functional analysis is required for novel and uncertain variants.
Marzieh Mohseni, Mojdeh Akbari, Kevin T. Booth, Mojgan Babanejad, Hela Azaiez, Fariba Ardalani, Sanaz Arzhangi, Khadijeh Jalalvand, Nooshin Nikzat, Fatemeh Ghodratpour,et al.
Springer Science and Business Media LLC
Zohreh Fattahi, Maryam Beheshtian, Marzieh Mohseni, Hossein Poustchi, Erin Sellars, Sayyed Hossein Nezhadi, Amir Amini, Sanaz Arzhangi, Khadijeh Jalalvand, Peyman Jamali,et al.
Hindawi Limited
Considering the application of human genome variation databases in precision medicine, population‐specific genome projects are continuously being developed. However, the Middle Eastern population is underrepresented in current databases. Accordingly, we established Iranome database (www.iranome.com) by performing whole exome sequencing on 800 individuals from eight major Iranian ethnic groups representing the second largest population of Middle East. We identified 1,575,702 variants of which 308,311 were novel (19.6%). Also, by presenting higher frequency for 37,384 novel or known rare variants, Iranome database can improve the power of molecular diagnosis. Moreover, attainable clinical information makes this database a good resource for classifying pathogenicity of rare variants. Principal components analysis indicated that, apart from Iranian‐Baluchs, Iranian‐Turkmen, and Iranian‐Persian Gulf Islanders, who form their own clusters, rest of the population were genetically linked, forming a super‐population. Furthermore, only 0.6% of novel variants showed counterparts in “Greater Middle East Variome Project”, emphasizing the value of Iranome at national level by releasing a comprehensive catalog of Iranian genomic variations and also filling another gap in the catalog of human genome variations at international level. We introduce Iranome as a resource which may also be applicable in other countries located in neighboring regions historically called Greater Iran (Persia).
Mojgan Babanejad, Masoud Motasaddi Zarandy, Nooshin Nikzat, Niloofar Bazazzadegan, Sanaz Arzhangi, Marzieh Mohseni, Kimia Kahrizi, and Hossein Najmabadi
Elsevier BV
Hao Hu, Kimia Kahrizi, Luciana Musante, Zohreh Fattahi, Ralf Herwig, Masoumeh Hosseini, Cornelia Oppitz, Seyedeh Sedigheh Abedini, Vanessa Suckow, Farzaneh Larti,et al.
Springer Science and Business Media LLC
Hoda Mehregan, Marzieh Mohseni, Khadijeh Jalalvand, Sanaz Arzhangi, Nooshin Nikzat, Sussan Banihashemi, Kimia Kahrizi, and Hossein Najmabadi
Elsevier BV
Zohreh Mehrjoo, Zohreh Fattahi, Maryam Beheshtian, Marzieh Mohseni, Hossein Poustchi, Fariba Ardalani, Khadijeh Jalalvand, Sanaz Arzhangi, Zahra Mohammadi, Shahrouz Khoshbakht,et al.
Public Library of Science (PLoS)
Iran, despite its size, geographic location and past cultural influence, has largely been a blind spot for human population genetic studies. With only sparse genetic information on the Iranian population available, we pursued its genome-wide and geographic characterization based on 1021 samples from eleven ethnic groups. We show that Iranians, while close to neighboring populations, present distinct genetic variation consistent with long-standing genetic continuity, harbor high heterogeneity and different levels of consanguinity, fall apart into a cluster of similar groups and several admixed ones and have experienced numerous language adoption events in the past. Our findings render Iran an important source for human genetic variation in Western and Central Asia, will guide adequate study sampling and assist the interpretation of putative disease-implicated genetic variation. Given Iran’s internal genetic heterogeneity, future studies will have to consider ethnic affiliations and possible admixture.
Kimia Kahrizi, Hao Hu, Masoumeh Hosseini, Vera M. Kalscheuer, Zohreh Fattahi, Maryam Beheshtian, Vanessa Suckow, Marzieh Mohseni, Bettina Lipkowitz, Sepideh Mehvari,et al.
Wiley
In outbred Western populations, most individuals with intellectual disability (ID) are sporadic cases, dominant de novo mutations (DNM) are frequent, and autosomal recessive ID (ARID) is very rare. Because of the high rate of parental consanguinity, which raises the risk for ARID and other recessive disorders, the prevalence of ID is significantly higher in near‐ and middle‐east countries. Indeed, homozygosity mapping and sequencing in consanguineous families have already identified a plethora of ARID genes, but because of the design of these studies, DNMs could not be systematically assessed, and the proportion of cases that are potentially preventable by avoiding consanguineous marriages or through carrier testing is hitherto unknown. This prompted us to perform whole‐exome sequencing in 100 sporadic ID patients from Iran and their healthy consanguineous parents. In 61 patients, we identified apparently causative changes in known ID genes. Of these, 44 were homozygous recessive and 17 dominant DNMs. Assuming that the DNM rate is stable, these results suggest that parental consanguinity raises the ID risk about 3.6‐fold, and about 4.1 to 4.25‐fold for children of first‐cousin unions. These results do not rhyme with recent opinions that consanguinity‐related health risks are generally small and have been “overstated” in the past.
Fariba Ranjzad, Nasser Aghdami, Ahmad Tara, Marzieh Mohseni, Reza Moghadasali, and Abbas Basiri
S. Karger AG
<b><i>Background/Aims:</i></b> Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited cystic kidney diseases caused by mutations in two large multi-exon genes, <i>PKD1</i> and <i>PKD2</i>. High allelic heterogeneity and duplication of <i>PKD1</i> exons 1–32 as six pseudo genes on chromosome 16 complicate molecular analysis of this disease. <b><i>Methods:</i></b> We applied targeted next-generation sequencing (NGS) in 9 non-consanguineous unrelated Iranian families with ADPKD to identify the genes hosting disease-causing mutations. This approach was confirmed by Sanger sequencing. <b><i>Results:</i></b> Here, we determined three different novel frameshift mutations and four previously reported nonsense mutations in the <i>PKD1</i> gene encoding polycystin1 in heterozygotes. <b><i>Conclusion:</i></b> This study demonstrates the effectiveness of NGS in significantly reducing the cost and time for simultaneous sequence analysis of PKD1 and PKD2, simplifying the genetic diagnostics of ADPKD. Although a probable correlation between the mutation types and phenotypic outcome is possible, however for more extensive studies in future, the consideration of renal hypouricemia (RHUC) and PKD1 coexistence may be helpful. The novel frameshift mutations reported by this study are p. Q1997X, P. D73X and p. V336X.
Mojgan Babanejad, Omid Ali Adeli, Nooshin Nikzat, Maryam Beheshtian, Hakimeh Azarafra, Farnaz Sadeghnia, Marzieh Mohseni, Hossein Najmabadi, and Kimia Kahrizi
Elsevier BV
Asal Honarpour, Marzieh Mohseni, Siamak Ghavidel Hajiagha, Shiva Irani, Hossein Najmabadi, , , , , and
CASRP: Center of Advanced Scientific Research and Publications
Received: 11 Oct. 2016 Accepted: 28 Jan. 2017