Molecular characterization of a large cohort of mucopolysaccharidosis patients: Iran Mucopolysaccharidosis RE-diagnosis study (IMPRESsion).

copy number variation geographical distribution lysosomal storage disorders mucopolysaccharidosis single nucleotide variant targeted next-generation sequencing

Journal

Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429

Informations de publication

Date de publication:
04 2022
Historique:
revised: 03 12 2021
received: 29 06 2021
accepted: 05 01 2022
pubmed: 11 1 2022
medline: 30 4 2022
entrez: 10 1 2022
Statut: ppublish

Résumé

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 reanalysis and confirmatory tests which confirmed MPS diagnosis in 104. Among the total of 258 MPS patients, 225 were homozygous, 90 harbored novel variants, and 9 had copy number variations. 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.962T>C [p.Leu321Pro], c.281C>A [p.Ser94*]), GALNS (c.319G>A [p.Ala107Thr], c.860C>T [p.Ser287Leu], c.1042A>G [p.Thr348Ala]), and IDUA (c.1A>C [p.Met1Leu], c.1598C>G [p.Pro533Arg], c.1562_1563insC [p.Gly522Argfs*50]). Our extensive patient cohort reveals the genetic and geographic landscape of MPS in Iran, which provides insight into genetic epidemiology of MPS and can facilitate a more cost-effective, time-efficient diagnostic approach based on the region-specific variants.

Identifiants

pubmed: 35005816
doi: 10.1002/humu.24328
doi:

Substances chimiques

Chondroitinsulfatases EC 3.1.6.-
GALNS protein, human EC 3.1.6.4

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1-e23

Informations de copyright

© 2022 Wiley Periodicals LLC.

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Auteurs

Saeed R Ghaffari (SR)

Department of Genomics, Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.
Department of Reproductive genetics, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
Department of Genomics, Gene Clinic, Tehran, Iran.

Maryam Rafati (M)

Department of Genomics, Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.
Department of Reproductive genetics, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Mahdi Shadnoush (M)

Department of Clinical Nutrition, Faculty of Nutrition & Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Shokooh Pourbabaee (S)

Deputy of Curative Affairs, Ministry of Health and Medical Education, Tehran, Iran.

Mohammad Aghighi (M)

Transplantation and Diseases Administration, Deputy of Curative Affairs, Ministry of Health and Medical Education, Tehran, Iran.

Siamak Mirab Samiee (S)

Food and Drug Laboratory Research Center, Ministry of Health and Medical Education, Tehran, Iran.
General Reference Health Laboratory, Ministry of Health and Medical Education, Tehran, Iran.

Jamshid Kermanchi (J)

Transplantation and Diseases Administration, Deputy of Curative Affairs, Ministry of Health and Medical Education, Tehran, Iran.

Mohammad R Alaei (MR)

Department of Pediatrics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Shadab Salehpour (S)

Department of Pediatrics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Davoud Amirkashani (D)

Division of Endocrinology and Metabolism, Ali-Asghar Children's Hospital, Iran University of Medical Sciences, Tehran, Iran.

Aria Setoodeh (A)

Children's Medical Center, Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Peymaneh Sarkhail (P)

Personalized Medicine and Genometabolomics Research Center, Hope Generation Foundation, Tehran, Iran.

Reza Shervin Badv (RS)

Department of Pediatrics, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.

Majid Aminzadeh (M)

Diabetes Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Khuzestan, Iran.

Siamak Shiva (S)

Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, East Azerbaijan, Iran.

Peyman Eshraghi (P)

Department of Pediatrics, Mashhad University of Medical Sciences, Mashhad, Khorasan Razavi, Iran.

Hossein Moravej (H)

Neonatal Research Center, Shiraz University of Medical Science, Shiraz, Fars, Iran.

Mahin Hashemipour (M)

Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Isfahan, Iran.

Noushin Rostampour (N)

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences Isfahan, Isfahan, Isfahan, Iran.

Amir Ali Hamidieh (AA)

Pediatric Cell and Gene Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Bibi Shahin Shamsian (BS)

Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Sedigheh Shams (S)

Department of Pathology, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.

Daniel Zamanfar (D)

Diabetes Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Ayoub Ebrahimi (A)

Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, East Azerbaijan, Iran.

Ali Otadi (A)

The University of British Columbia, Faculty of Science, Vancouver, British Columbia, Canada.

Seyedeh Zahra Tara (SZ)

Pediatric Endocrinology Department, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Zeinab Barati (Z)

Department of Genomics, Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.
Department of Reproductive genetics, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Laya Fakhri (L)

Department of Genomics, Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.
Department of Reproductive genetics, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Azadeh Hoseini (A)

Department of Reproductive genetics, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Hosna Amiri (H)

Department of Reproductive genetics, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Somayeh Ramandi (S)

Department of Reproductive genetics, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Niusha Mostofinezhad (N)

Department of Reproductive genetics, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Zahra Pahlevani Kani (ZP)

Islamic Azad University Tehran Medical Sciences, Tehran, Tehran, Iran.

Elham Mohammadyari (E)

Islamic Azad University Tehran Medical Sciences, Tehran, Tehran, Iran.

Mahsa Khosravi (M)

Islamic Azad University Tehran Medical Sciences, Tehran, Tehran, Iran.

Masoome Saadati (M)

Islamic Azad University Tehran North Branch, Tehran, Tehran, Iran.

Fatemeh Hoseininasab (F)

Department of Reproductive genetics, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Hamid Reza Khorram Khorshid (HR)

Department of Genomics, Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.

Younes Modaberisaber (Y)

Department of Genomics, Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.

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