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Molecular characterization of a large cohort of Mucopolysaccharidosis patients: Iran Mucopolysaccharidosis RE-diagnosis Study (IMPRESsion)
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  • Saeed Ghaffari,
  • Maryam Rafati,
  • Mahdi Shadnoush,
  • Shokooh Pourbabaee,
  • Mohammad Aghighi,
  • Siamak Mirab Samiee,
  • Jamshid Kermanchi,
  • Mohammad Reza Alaei,
  • Shadab Salehpoor,
  • Davoud Amirkashani,
  • Aria Sotoodeh,
  • Peymaneh Sarkhail,
  • Reza Shervin Badv,
  • Majid Aminzadeh,
  • Siamak Shiva,
  • Peyman Eshraghi,
  • Hossein Moravej,
  • Mahin Hashemipour,
  • Noushin Rostampour,
  • Amir Ali Hamidieh,
  • Bibi Shahin Shamsian,
  • Sedigheh Shams,
  • Daniel Zamanfar,
  • Ayoub Ebrahimi,
  • Ali Otadi,
  • Seyedeh Zahra Tara,
  • Zeinab Barati,
  • Laya Fakhri,
  • Azadeh Hosseini,
  • Hosna Amiri,
  • Somayeh Ramandi,
  • Niusha Mostofinezhad,
  • Zahra Pahlevani Kani,
  • Elham Mohammadyari,
  • Mahsa Khosravi,
  • Masoome Saadati,
  • Fatemeh Hoseininasab,
  • Hamid Reza Khorram Khorshid,
  • Younes Modaberisaber
Saeed Ghaffari
Hope Generation Foundation

Corresponding Author:saeed@ghaffari.org

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Maryam Rafati
Hope Generation Foundation
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Mahdi Shadnoush
Shahid Beheshti University of Medical Sciences
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Shokooh Pourbabaee
Iran Ministry of Health and Medical Education
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Mohammad Aghighi
Iran Ministry of Health and Medical Education
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Siamak Mirab Samiee
Iran Ministry of Health and Medical Education
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Jamshid Kermanchi
Iran Ministry of Health and Medical Education
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Mohammad Reza Alaei
Shahid Beheshti University of Medical Sciences
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Shadab Salehpoor
Shahid Beheshti University of Medical Sciences
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Davoud Amirkashani
Iran University of Medical Sciences
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Aria Sotoodeh
Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
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Peymaneh Sarkhail
Hope Generation Foundation
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Reza Shervin Badv
Tehran University of Medical Sciences
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Majid Aminzadeh
Ahvaz Jundishapur University
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Siamak Shiva
Tabriz University of Medical Sciences
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Peyman Eshraghi
Mashhad University of Medical Sciences
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Hossein Moravej
Shiraz University of Medical Sciences
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Mahin Hashemipour
Isfahan University of Medical Sciences
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Noushin Rostampour
Isfahan University of Medical Sciences Isfahan Endocrine and Metabolism Research Center
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Amir Ali Hamidieh
Tehran University of Medical Sciences
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Bibi Shahin Shamsian
Shahid Beheshti University of Medical Sciences
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Sedigheh Shams
Tehran University of Medical Sciences
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Daniel Zamanfar
Mazandaran University of Medical Sciences
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Ayoub Ebrahimi
Tabriz University of Medical Sciences
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Ali Otadi
The University of British Columbia Faculty of Science
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Seyedeh Zahra Tara
The Children's Hospital of Philadelphia
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Zeinab Barati
Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR)
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Laya Fakhri
Hope Generation Foundation
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Azadeh Hosseini
Hope Generation Foundation
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Hosna Amiri
Hope Generation Foundation
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Somayeh Ramandi
Hope Generation Foundation
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Niusha Mostofinezhad
Hope Generation Foundation
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Zahra Pahlevani Kani
Islamic Azad University Tehran Medical Sciences
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Elham Mohammadyari
Islamic Azad University Tehran Medical Sciences
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Mahsa Khosravi
Islamic Azad University Tehran Medical Sciences
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Masoome Saadati
Islamic Azad University Tehran North Branch
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Fatemeh Hoseininasab
Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR)
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Hamid Reza Khorram Khorshid
Hope Generation Foundation
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Younes Modaberisaber
Hope Generation Foundation
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Abstract

Mucopolysaccharidoses (MPSs) are rare, heterogeneous inborn errors of metabolism (IEM) diagnosed through a combination of clinical, biochemical, and genetic investigations. The aim of this study was molecular characterization of the largest cohort of Iranian MPS patients (302 patients from 289 unrelated families), along with tracking their ethnicity and geographical origins. 185/289 patients were studied using an IEM-targeted NGS panel followed by complementary Sanger sequencing, which led to the diagnosis of 154 MPS patients and 5 non-MPS IEMs (diagnostic yield: 85.9%). Furthermore, 106/289 patients who were referred with positive findings went through re-analysis and confirmatory tests which confirmed MPS diagnosis in 104. Among the total of 258 MPS patients, 225 were homozygous, and 9 had copy number variations, and 90 had novel variants. MPS IV was the most common type (34.8%) followed by MPS I (22.7%) and MPS VI (22.5%). Geographical origin analysis unveiled a pattern of distribution for frequent variants in ARSB (c.430G>A, c.962C>T, c.281C>A), GALNS (c.319G>A, c.860C>T, c.1042A>G), and IDUA (c.1A>C, c.1598C>G). Our extensive patient cohort reveals the genetic and geographic landscape of MPS in Iran, which provides insight into the genetic epidemiology of MPS and can facilitate a more cost-effective, time-efficient diagnostic approach based on the region-specific variants.
27 Jun 2021Submitted to Human Mutation
30 Jun 2021Submission Checks Completed
30 Jun 2021Assigned to Editor
22 Jul 2021Reviewer(s) Assigned
22 Aug 2021Review(s) Completed, Editorial Evaluation Pending
27 Aug 2021Editorial Decision: Revise Major
03 Dec 20211st Revision Received
03 Dec 2021Submission Checks Completed
03 Dec 2021Assigned to Editor
07 Dec 2021Reviewer(s) Assigned
20 Dec 2021Review(s) Completed, Editorial Evaluation Pending
05 Jan 2022Editorial Decision: Accept
Apr 2022Published in Human Mutation volume 43 issue 4. 10.1002/humu.24328