Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I

Taghikhani, Mohammad; Khatami, Shohreh; Abdi, Mohammad; Hakhamaneshi, Mohammad Said; Alaei, Mohammad Reza; Zamanfar, Daniel; Vakili, Rahim

doi:10.1002/jcla.22963

Cited by 6 publications

(5 citation statements)

References 19 publications

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“…Biochemical assays already described for these variants showed essentially no activity in homozygotes (13), concord-ant with Hurler phenotype, in our patients being observed a very low activity for the enzyme, the clinical phenotype being also Hurler syndrome. The incidence of p.Q70* (c.208C>T) mutation, 3/8 alleles of pathological variants of IDUA gene alleles identified in our group is according to results reported by other studies (5,(14)(15)(16)(17)(18)(19). In F4, compound heterozygous p.Q70*(c.208C>T), the second variant is a deletion located on exon 1 (p.S16_A19del, 46_57delTCGCTCCTGGCC), described by Bunge in 1994, as a mutation that induces a severe phenotype (3,20).…”

Section: Discussionsupporting

confidence: 89%

Mucopolysaccharidosis type I - Clinical and genetic characteristics of Romanian patients

Alkhzouz

Lazea

Miclea

et al. 2020

Revista Romana De Medicina De Laborator

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Background: Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by a deficiency of α-L-iduronidase (IDUA), which leads to the accumulation of partially digested glycosaminoglycans (dermatan sulfate and heparan sulfate) in the lysosomes and induces multisystemic alteration. Hurler (severe), Scheie (mild), and Hurler/Scheie (intermediate) syndromes are clinical subtypes of MPS-I. To date, more than 290 IDUA mutations have been reported. The purpose of this study was to present the clinical and genetic characteristics of Romanian MPS I syndrome patients and their genotype-phenotype correlation.Patients and methods: Seven patients (5 girls and 2 boys) with MPS type I, belonging to 4 unrelated families, aged 0,75-17.9 years, were enrolled. The study methods consisted in: clinical and standard auxological assessment, bone radiographs, joint ultrasonography, goniometry, neurological and psychological evaluation, hepatic and splenic ultrasonography, cardiological evaluation, otorhinolaryngology examination, ophthalmological examination, spirometry, α-L-iduronidase enzyme activity assay and molecular analysis.Results: The seven patients originated from 4 unrelated families, three patients with severe, two patients with intermediate and two with attenuated clinical phenotype. Each patient presented the classical picture of MPS type I picture, represented by: variable coarse facial features, arthropathy, hepatosplenomegaly, cardiac involvement, respiratory dysfunction and neurological impairment. Five patological variants, three point mutations (p.Q70 *, p.I238Q and p.K324R), two deletion c.1045_1047delGAC, c.46_57delTCGCTCCTG) and an insertion (c.1389 insC) were identified in both alleles of the ADUA gene in homozygous or heterozygous form. Two novel mutations (p.K324R and c.1389 insC) were reported. The p.Q70*(c.208C>T) variant was identified in 2 families with severe form of disease (Hurler syndrome) in homozygous status in one family and in compound heterozygous status in the other family.Conclusion: The p.Q70* missense variant was the most frequent, correlated in all the cases who presented it with severe form, Hurler syndrome, the other mutations being usually isolated and particular for each patient, associated in our patients with less severe MPS I phenotype, as Hurler-Scheie or Scheie syndrome. The results of this study indicated the mutational heterogeneity of the IDUA gene and the difficulty to indicate some correlation between the genotype and phenotype in MPS I patients.

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Section: Discussionsupporting

confidence: 89%

Mucopolysaccharidosis type I - Clinical and genetic characteristics of Romanian patients

Alkhzouz

Lazea

Miclea

et al. 2020

Revista Romana De Medicina De Laborator

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“…There are recently published mutations specific for some nations, including Yemen (c.657delA) [ 69 ], Pakistan (p.L303P and c.1456G > T) [ 54 , 70 ], and Tunisia (c.1650 + 1G > T) [ 71 ]. Additionally, Iran has the novel widespread mutation p.Y109H, which accounts for 15.6% of identified mutations [ 72 ].…”

Section: Mutationsmentioning

confidence: 99%

Epidemiology of Mucopolysaccharidoses Update

Çelik

Tomatsu

et al. 2021

Diagnostics

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Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a lysosomal enzyme deficiency or malfunction, which leads to the accumulation of glycosaminoglycans in tissues and organs. If not treated at an early stage, patients have various health problems, affecting their quality of life and life-span. Two therapeutic options for MPS are widely used in practice: enzyme replacement therapy and hematopoietic stem cell transplantation. However, early diagnosis of MPS is crucial, as treatment may be too late to reverse or ameliorate the disease progress. It has been noted that the prevalence of MPS and each subtype varies based on geographic regions and/or ethnic background. Each type of MPS is caused by a wide range of the mutational spectrum, mainly missense mutations. Some mutations were derived from the common founder effect. In the previous study, Khan et al. 2018 have reported the epidemiology of MPS from 22 countries and 16 regions. In this study, we aimed to update the prevalence of MPS across the world. We have collected and investigated 189 publications related to the prevalence of MPS via PubMed as of December 2020. In total, data from 33 countries and 23 regions were compiled and analyzed. Saudi Arabia provided the highest frequency of overall MPS because of regional or consanguineous marriages (or founder effect), followed by Portugal, Brazil, the Netherlands, and Australia. The newborn screening is an efficient and early diagnosis for MPS. MPS I has been approved for newborn screening in the United States. After the newborn screening of MPS I, the frequency of MPS I increased, compared with the past incidence rates. Overall, we conclude that the current identification methods are not enough to recognize all MPS patients, leading to an inaccurate incidence and status. Differences in ethnic background and/or founder effects impact on the frequency of MPS, which affects the prevalence of MPS. Two-tier newborn screening has accelerated early recognition of MPS I, providing an accurate incidence of patients.

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“…Although there have been a few studies published in recent years that have contributed to our understanding of the molecular causes of MPS in Iran, the patient pool in those studies was considerably smaller than that of ours. Overall, 18 studies have reported molecular characterization of Iranian MPS patients, comprising 46 MPS I patients, 34 MPS VI patients, 19 MPS III patients, 4 MPS II patients, 4 MPS IV patients, and 1 MPS VII patient (Abbasi et al, 2017; Alaei et al, 2020; Aminzadeh et al, 2019; Jafaryazdi et al, 2019; Kamranjam & Alaei, 2019; Khorrami et al, 2019; Malekpour et al, 2018; Mansour et al, 2007; Martins et al, 2019; Mosallanejad et al, 2020; Nouri et al, 2012; Salehi, 2004; Seyedhassani et al, 2015; Shafaat et al, 2020; Taghikhani et al, 2019; Valstar, Bertoli‐Avella, et al, 2010; Yassaee et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Variome MPS Database Alaei et al, 2020;Aminzadeh et al, 2019;Jafaryazdi et al, 2019;Kamranjam & Alaei, 2019;Khorrami et al, 2019;Malekpour et al, 2018;Mansour et al, 2007;Martins et al, 2019;Mosallanejad et al, 2020;Nouri et al, 2012;Salehi, 2004;Seyedhassani et al, 2015;Shafaat et al, 2020;Taghikhani et al, 2019;Valstar, Bertoli-Avella, et al, 2010;Yassaee et al, 2017). American Caucasian, Austrian, Macedonian, Turkish, Greek, and Indian population (Bidchol et al, 2014;Morrone et al, 2014).…”

Section: Details Of the Variants Identified In This Study Are Availab...mentioning

confidence: 99%

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

et al. 2022

Self Cite

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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.

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Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I

Cited by 6 publications

References 19 publications

Mucopolysaccharidosis type I - Clinical and genetic characteristics of Romanian patients

Mucopolysaccharidosis type I - Clinical and genetic characteristics of Romanian patients

Epidemiology of Mucopolysaccharidoses Update

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

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