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 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.
Subject(s)
Chondroitinsulfatases , Mucopolysaccharidoses , Mucopolysaccharidosis I , Mucopolysaccharidosis VI , Chondroitinsulfatases/genetics , DNA Copy Number Variations , Humans , Iran/epidemiology , Mucopolysaccharidoses/diagnosis , Mucopolysaccharidoses/genetics , Mucopolysaccharidosis I/diagnosis , Mucopolysaccharidosis I/epidemiology , Mucopolysaccharidosis I/genetics , Mucopolysaccharidosis VI/geneticsABSTRACT
Hyperostosis-hyperphosphataemia syndrome (HHS) is a rare autosomal recessive metabolic disorder, characterized by recurrent painful swelling of long bones, periosteal new bone formation and cortical hyperostosis or intramedullary sclerosis, hyperphosphatemia and low intact fibroblast growth factor 23 (FGF23) protein levels. It is caused by mutations in 2 genes, N-acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3) and FGF23. We have performed mutation analysis of the GALNT3 and FGF23 genes in a patient with HHS and detected a homozygous mutation in exon 3 of FGF23 gene (NM_020638.2: c.471C>A) which results in amino acid change from phenylalanine 157 to leucin (p.F157L) in receptor interaction site.
Subject(s)
Fibroblast Growth Factors/genetics , Hyperostosis/genetics , Hyperphosphatemia/genetics , Mutation, Missense , Amino Acid Substitution , Child, Preschool , Computer Simulation , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/chemistry , Homozygote , Humans , Male , N-Acetylgalactosaminyltransferases/genetics , Protein Conformation , Polypeptide N-acetylgalactosaminyltransferaseABSTRACT
BACKGROUND: Human papilloma virus causes benign and malignant abnormalities in different part of the body. The link between high risk types of HPV and some anogenital and aerodigestive tract cancer is well established. Oral HPV infection plays a role in developing oropharyngeal squamous cell carcinoma. We studied the prevalence of oral HPV in healthy individuals and its relative risk factors. METHODS: Saliva samples of 114 healthy subjects were collected for HPV DNA analysis. Volunteers completed questionnaires and signed a written consent. For data analysis descriptive statistic, chi square test and odds ratio was used. RESULTS: The frequency of oral HPV in healthy individuals was 6.1 %(seven participant).The most frequent type was HPV-18 in five of them. HPV-6 and HPV-66 each was detected in one case. Relation of oral HPV positivity to demographic features and risk factors was not statistically significant. CONCLUSIONS: The prevalence of oral HPV infection in our community is the same as many other communities of developing countries, stressing that HPV-18 were the dominant type.
