{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:01:20Z","timestamp":1753891280859,"version":"3.41.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Mucopolysaccharidoses are a group of lysosomal storage disorders that include seven types that are classified based on the enzymes that are disrupted. Malfunction of these enzymes leads to the accumulation of glycosaminoglycans (GAGs) in various tissues. Due to genetic and clinical heterogeneity, diagnosing and distinguishing the different types is challenging. Genetic methods such as whole exome sequencing (WES) and Sanger sequencing are accurate methods for detecting pathogenic variants in patients. <\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Thirty-two cases of mucopolysaccharidosis, predominantly from families with consanguineous marriages, were genetically examined. Out of these, fourteen cases underwent targeted sequencing, while the rest underwent WES. The results of WES were analyzed and the pathogenicity of the variants was examined using bioinformatics tools. In addition, a segregation analysis within families was carried out.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In most cases, a pathogenic or likely pathogenic variant was detected. Sixteen previously reported variants and six new variants were detected in the known <jats:italic>IDS<\/jats:italic> (c.458G&amp;gt;C, c.701del, c.920T&amp;gt;G), <jats:italic>GNS<\/jats:italic> (c.1430A&amp;gt;T), <jats:italic>GALNS<\/jats:italic> (c.1218_1221dup), and <jats:italic>SGSH<\/jats:italic> (c.149T&amp;gt;C) genes. Furthermore, we discovered a c.259G&amp;gt;C substitution in the <jats:italic>NAGLU<\/jats:italic> gene for the first time in three homozygous patients. This substitution was previously reported as heterozygous. Except for the variants related to the <jats:italic>IDS<\/jats:italic> gene, which were hemizygous, all the other variants were homozygous.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> It appears that the high rate of consanguineous marriages in the families being studied has had a significant impact on the occurrence of this disease. Overall, these findings could expand the spectrum of pathogenic variants in mucopolysaccharidoses. Genetic methods, especially WES, are very accurate and can be used alone or in conjunction with other diagnostic methods for a more precise and rapid diagnosis of mucopolysaccharidoses. Additionally, they could be beneficial for family screening and disease prevention.<\/jats:p>","DOI":"10.3389\/fgene.2024.1343094","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T11:48:52Z","timestamp":1707997732000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of new variants in patients with mucopolysaccharidosis in consanguineous Iranian families"],"prefix":"10.3389","volume":"15","author":[{"given":"Rezvan","family":"Zabihi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mina","family":"Zamani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majid","family":"Aminzadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niloofar","family":"Chamanrou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatemeh Zahra","family":"Kiani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahere","family":"Seifi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jawaher","family":"Zeighami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahere","family":"Yadegari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alireza","family":"Sedaghat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alihossein","family":"Saberi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Hamid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gholamreza","family":"Shariati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid","family":"Galehdari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods."},{"key":"B2","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1007\/s10545-006-0403-z","article-title":"Molecular characterization of Portuguese patients with mucopolysaccharidosis type II shows evidence that the IDS gene is prone to splicing mutations","volume":"29","author":"Alves","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.gene.2019.04.050","article-title":"Identification of arylsulfatase B gene mutations and clinical presentations of Iranian patients with Mucopolysaccharidosis VI","volume":"706","author":"Aminzadeh","year":"2019","journal-title":"Gene"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e1004962","DOI":"10.1371\/journal.pcbi.1004962","article-title":"PredictSNP2: a unified platform for accurately evaluating SNP effects by exploiting the different characteristics of variants in distinct genomic regions","volume":"12","author":"Bendl","year":"2016","journal-title":"PLoS Comput. Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"E2189","DOI":"10.1002\/humu.21479","article-title":"IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel \u03b1-L-iduronidase (IDUA) alleles","volume":"32","author":"Bertola","year":"2011","journal-title":"Hum. Mutat."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1002\/ajmg.a.36735","article-title":"GALNS mutations in Indian patients with mucopolysaccharidosis IVA","author":"Bidchol","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"B7","first-page":"28","article-title":"Mucopolysaccharidosis type IIIB (Sanfilippo B): identification of 18 novel alpha-N-acetylglucosaminidase gene mutations","volume":"36","author":"Bunge","year":"1999","journal-title":"Med. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"273","DOI":"10.3390\/diagnostics11020273","article-title":"Epidemiology of mucopolysacchari doses update","volume":"11","author":"\u00c7elik","year":"2021","journal-title":"Diagn. (Basel)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/(SICI)1098-1004(1998)11:4<313::AID-HUMU9>3.0.CO;2-P","article-title":"Identification of molecular defects in Italian Sanfilippo A patients including 13 novel mutations","volume":"11","author":"Di Natale","year":"1998","journal-title":"Hum. Mutat."},{"key":"B10","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1086\/508068","article-title":"Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C)","volume":"79","author":"Fan","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"B34","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/j.1651-2227.2007.00213.x","article-title":"Mucopolysaccharidosis type II: an update on mutation spectrum","volume":"96","author":"Froissart","year":"2007","journal-title":"Acta Paediatr."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.3390\/cells9081838","article-title":"Mucopolysaccharidosis type I: a review of the natural history and molecular pathology","volume":"9","author":"Hampe","year":"2020","journal-title":"Cells"},{"key":"B12","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1086\/508294","article-title":"Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome)","volume":"79","author":"Hreb\u00edcek","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1007\/s004390050901","article-title":"Mutational spectrum of the iduronate-2-sulfatase (IDS) gene in 36 unrelated Russian MPS II patients","volume":"103","author":"Karsten","year":"1998","journal-title":"Hum. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat. Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: the human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"key":"B16","doi-asserted-by":"publisher","first-page":"172","DOI":"10.3390\/diagnostics10030172","article-title":"Diagnosis of mucopolysaccharidoses","volume":"10","author":"Kubaski","year":"2020","journal-title":"Diagnostics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"E3","DOI":"10.1136\/jmg.39.2.e3","article-title":"Identification and characterisation of mutations underlying Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB)","volume":"39","author":"Lee-Chen","year":"2002","journal-title":"J. Med. Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1023\/a:1005335624386","article-title":"Molecular analysis in 23 Hunter disease families","volume":"20","author":"Lissens","year":"1997","journal-title":"J. Inherit. Metab. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1002\/humu.23752","article-title":"Molecular characterization of a large group of Mucopolysaccharidosis type IIIC patients reveals the evolutionary history of the disease","volume":"40","author":"Martins","year":"2019","journal-title":"Hum. Mutat."},{"key":"B20","doi-asserted-by":"publisher","first-page":"100874","DOI":"10.1016\/j.spen.2021.100874","article-title":"Update in the mucopolysaccharidoses","volume":"37","author":"McBride","year":"2021","journal-title":"Semin. Pediatr. Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells","volume":"16","author":"Miller","year":"1988","journal-title":"Nucleic Acids Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1093\/rheumatology\/ker394","article-title":"Overview of the mucopolysaccharidoses","volume":"50","author":"Muenzer","year":"2011","journal-title":"Rheumatol. Oxf."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.4103\/ijo.IJO_425_22","article-title":"Mucopolysaccharidosis: a broad review","volume":"70","author":"Nagral","year":"2022","journal-title":"Indian J. Ophthalmol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s10545-012-9533-7","article-title":"Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations","volume":"36","author":"Pollard","year":"2013","journal-title":"J. Inherit. Metab. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1007\/s40265-019-01147-4","article-title":"Therapeutic options for mucopolysaccharidoses: current and emerging treatments","volume":"79","author":"Sawamoto","year":"2019","journal-title":"Drugs"},{"key":"B26","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1086\/301685","article-title":"NAGLU mutations underlying Sanfilippo syndrome type B","volume":"62","author":"Schmidtchen","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"W446","DOI":"10.1093\/nar\/gkab266","article-title":"MutationTaster2021","volume":"49","author":"Steinhaus","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1002\/humu.23613","article-title":"Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: review and classification of published variants in the ARSB gene","volume":"39","author":"Tomanin","year":"2018","journal-title":"Hum. Mutat."},{"key":"B29","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1111\/j.1399-0004.1981.tb01821.x","article-title":"Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B, and C)","volume":"20","author":"van de Kamp","year":"1981","journal-title":"Clin. Genet."},{"key":"B30","doi-asserted-by":"publisher","first-page":"108392","DOI":"10.1016\/j.mrrev.2021.108392","article-title":"A molecular genetics view on Mucopolysaccharidosis Type II","volume":"788","author":"Verma","year":"2021","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/BF00212019","article-title":"Four novel mutant alleles of the arylsulfatase B gene in two patients with intermediate form of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)","volume":"93","author":"Voskoboeva","year":"1994","journal-title":"Hum. Genet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1002\/humu.1189","article-title":"Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: diagnostic, clinical, and biological implications","volume":"18","author":"Yogalingam","year":"2001","journal-title":"Hum. Mutat."},{"key":"B33","doi-asserted-by":"publisher","first-page":"100658","DOI":"10.1016\/j.ymgmr.2020.100658","article-title":"A case of mucopolysaccharidosis type VI in a polish family. Importance of genetic testing and genotype-phenotype relationship in the diagnosis of mucopolysaccharidosis","volume":"25","author":"Zapa\u0142a","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.cca.2019.01.009","article-title":"Genetic analysis of 63 Chinese patients with mucopolysaccharidosis type II: Functional characterization of seven novel IDS variants","volume":"491","author":"Zhang","year":"2019","journal-title":"Clin. Chim. Acta."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2024.1343094\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T11:48:57Z","timestamp":1707997737000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2024.1343094\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,15]]},"references-count":35,"alternative-id":["10.3389\/fgene.2024.1343094"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2024.1343094","relation":{},"ISSN":["1664-8021"],"issn-type":[{"type":"electronic","value":"1664-8021"}],"subject":[],"published":{"date-parts":[[2024,2,15]]},"article-number":"1343094"}}