Deep Genotyping of the IDS Gene in Colombian Patients with Hunter Syndrome

Galvis, Johanna Aristizábal; González, Jannet; Uribe, Alfredo; Velasco, Harvy

doi:10.1007/8904_2014_376

Cited by 16 publications

(24 citation statements)

References 47 publications

(55 reference statements)

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“…Patient with p.Asn63Asp showed attenuated phenotype in our study, similar to earlier report. p.Gly140Arg was reported to be associated with mild phenotype in Japanese MPS II patients whereas it is associated with severe phenotype in Indian MPS II patient . In our study, patient with p.Ser143Phe showed attenuated phenotype due to IDS structural distortion caused from substitution of a small polar Serine to a large non‐polar Phenyl alanine.…”

Section: Discussionmentioning

confidence: 51%

“…In our study, patient with p.Ser143Phe showed attenuated phenotype due to IDS structural distortion caused from substitution of a small polar Serine to a large non-polar Phenyl alanine. p.Arg468Gln was known to be associated with a severe phenotype as a basic polar Arginine was substituted by a neutral Glutamine (25). This pathogenic variant in two Indian MPS II patients showed the phenotypes ranging from attenuated to severe forms unlike the previous reports.…”

Section: Hurler Syndromementioning

confidence: 70%

“…Patients with p.Ile485Arg showed severe phenotype in Indian patient group. In comparison to the mutation spectrum in Indian population, p.Arg468Gln, p.Gln465*, p.Lys347Gln, p.Lys236Asn, p.Arg88His and p.Ser71Asn were frequent pathogenic variants (53.8%) reported in Columbian and Austrian populations .…”

Section: Discussionmentioning

confidence: 90%

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Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II

et al. 2016

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Mucopolysaccharidoses (MPS), a subgroup of lysosomal storage disorders, are caused due to deficiency of specific lysosomal enzyme involved in catabolism of glycosaminoglycans. To date more than 200 pathogenic variants in the alpha-l-iduronidase (IDUA) for MPS I and ∼500 pathogenic variants in the iduronate-2-sulphatase (IDS) for MPS II have been reported worldwide. The mutation spectrum of MPS type I and MPS type II disorders in Indian population is not characterized yet. In this study, we carried out clinical, biochemical, molecular and in silico analyses to establish the mutation spectrum of MPS I and MPS II in the Indian population. We conducted molecular analysis for 60 MPS-affected patients [MPS I (n = 30) (Hurler syndrome = 17, Hurler-Scheie syndrome = 13), and MPS II (n = 30) (severe = 18, attenuated = 12)] and identified a total of 44 [MPS I (n = 22) and MPS II (n = 22)] different pathogenic variants comprising missense, nonsense, frameshift, gross deletions and splice site variants. A total of 20 [MPS I (n = 14), and MPS II (n = 6)] novel pathogenic sequence variants were identified in our patient cohort. We found that 32% of pathogenic variants detected in IDUA were recurrent and 25% in MPS II. This is the first study revealing the mutation spectrum of MPS I and MPS II patients in the Indian population.

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Section: Discussionmentioning

confidence: 51%

Section: Hurler Syndromementioning

confidence: 70%

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Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II

et al. 2016

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“…It is also the only reliable way to identify female carriers of the disease which is a critical factor in family planning decisions [4]. Mutations identified in the patients included large alterations and small gene alterations which further confirmed the extreme heterogeneity of IDS gene alterations, as more than 350 have been reported to date [5, 6]. …”

Section: Introductionmentioning

confidence: 77%

Clinical, biochemical and molecular characteristics of Filipino patients with mucopolysaccharidosis type II - Hunter syndrome

Chiong

Canson

Abacan

et al. 2017

Orphanet J Rare Dis

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BackgroundMucopolysaccharidosis type II, an X-linked recessive disorder is the most common lysosomal storage disease detected among Filipinos. This is a case series involving 23 male Filipino patients confirmed to have Hunter syndrome. The clinical and biochemical characteristics were obtained and mutation testing of the IDS gene was done on the probands and their female relatives.ResultsThe mean age of the patients was 11.28 (SD 4.10) years with an average symptom onset at 1.2 (SD 1.4) years. The mean age at biochemical diagnosis was 8 (SD 3.2) years. The early clinical characteristics were developmental delay, joint stiffness, coarse facies, recurrent respiratory tract infections, abdominal distention and hernia. Majority of the patients had joint contractures, severe intellectual disability, error of refraction, hearing loss and valvular regurgitation on subspecialists’ evaluation. The mean GAG concentration was 506.5 mg (SD 191.3)/grams creatinine while the mean plasma iduronate-2-sulfatase activity was 0.86 (SD 0.79) nmol/mg plasma/4 h. Fourteen (14) mutations were found: 6 missense (42.9%), 4 nonsense (28.6%), 2 frameshift (14.3%), 1 exon skipping at the cDNA level (7.1%), and 1 gross insertion (7.1%). Six (6) novel mutations were observed (43%): p.C422F, p.P86Rfs*44, p.Q121*, p.L209Wfs*4, p.T409R, and c.1461_1462insN[710].ConclusionThe age at diagnosis in this series was much delayed and majority of the patients presented with severe neurologic impairment. The results of the biochemical tests did not contribute to the phenotypic classification of patients. The effects of the mutations were consistent with the severe phenotype seen in the majority of the patients.

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“…(Pro467Leu)Severe (P24)Phenotype not reported [22]c.1403G>Ap. (Arg468Gln)Severe (P20)Severe [71]; severe [57]; severe [67]; four severe patients [63]; severe [34]; three severe patients [35]; severe [31]; severe [25]; severe [18]c.1478G>Cp. (Arg493Pro)Severe (P17)Phenotype not reported [46]SGSHc.197C>Gp.…”

Section: Resultsmentioning

confidence: 99%

Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study

et al. 2019

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Mucopolysaccharidoses (MPS) are a subgroup of 11 monogenic lysosomal storage disorders due to the deficit of activity of the lysosomal hydrolases deputed to the degradation of mucopolysaccharides. Although individually rare, all together they account for at least 1:25,000 live births. In this study, we present the genetic analysis of a population of 71 MPS patients enrolled in a multicenter Italian study. We re-annotated all variants, according to the latest recommendations, and re-classified them as suggested by the American College of Medical Genetics and Genomics. Variant distribution per type was mainly represented by missense mutations. Overall, 10 patients had received no molecular diagnosis, although 6 of them had undergone either HSCT or ERT, based on clinical and enzymatic evaluations. Moreover, nine novel variants are reported. Conclusions : Our analysis underlines the need to complete the molecular diagnosis in patients previously diagnosed only on a biochemical basis, suggests a periodical re-annotation of the variants and solicits their deposition in public databases freely available to clinicians and researchers. We strongly recommend a molecular diagnosis based on the analysis of the “trio” instead of the sole proband. These recommendations will help to obtain a complete and correct diagnosis of mucopolysaccharidosis, rendering also possible genetic counseling. What is known • MPS are a group of 11 metabolic genetic disorders due to deficits of enzymes involved in the mucopolysaccharides degradation. • Molecular analysis is commonly performed to confirm enzymatic assays. What is new • Eighty-six percent of the 71 patients we collected received a molecular diagnosis; among them, 9 novel variants were reported. • We stress the importance of molecular diagnosis in biochemically diagnosed patients, encourage a periodical re-annotation of variants according to the recent nomenclature and their publication in open databases. Electronic supplementary material The online version of this article (10.1007/s00431-019-03341-8) contains supplementary material, which is available to authorized users.

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Deep Genotyping of the IDS Gene in Colombian Patients with Hunter Syndrome

Abstract: The frequency of novel mutations (46.15%) is similar to what has been reported elsewhere. The use of bioinformatic tools showed differences in enzyme-substrate interactions. Studies with larger groups of patients are needed.

Cited by 16 publications

References 47 publications

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II

Clinical, biochemical and molecular characteristics of Filipino patients with mucopolysaccharidosis type II - Hunter syndrome

Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study

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