Identification of 11 novel mutations in 49 Korean patients with mucopolysaccharidosis type II

Yb, Sohn; Cs, Ki; Ch, Kim; Ar, Ko; Yj, Yook; Sj, Lee; Sj, Kim; Sw, Park; Yeau, Sung-Hee; Ek, Kwon; Han, SJ; Choi, Eung‐Chil; Lee, Soo-Youn; Jw, Kim; Jin, Di

doi:10.1111/j.1399-0004.2011.01641.x

Cited by 26 publications

(30 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also detected a disease-associated SNP predicted to enhance miR-124 binding within an exonic Ago2 cluster in the IDS gene encoding iduronate 2-sulfatase. The prospect that this may augment the repression of iduronate 2-sulfatase expression is interesting considering that the mutation causes an enzyme deficiency resulting in an attenuated form of Hunter syndrome (Sohn et al, 2012). …”

Section: Resultsmentioning

confidence: 99%

Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain

Boudreau

Jiang

Gilmore

et al. 2014

Neuron

195

207

View full text Add to dashboard Cite

Summary The orchestration of brain function requires complex gene regulatory networks that are modulated, in part, by microRNAs (miRNAs). These noncoding RNAs associate with argonaute (Ago) proteins in order to direct posttranscriptional gene suppression via base pairing with target transcripts. In order to better understand how miRNAs contribute to human-specialized brain processes and neurological phenotypes, identifying their targets is of paramount importance. Here, we address the latter by profiling Ago2:RNA interactions using HITS-CLIP to generate a transcriptome-wide map of miRNA binding sites in human brain. We uncovered ∼7,000 stringent Ago2 binding sites that are highly enriched for conserved sequences corresponding to abundant brain miRNAs. This interactome points to functional miRNA:target pairs across >3,000 genes and represents a valuable resource for accelerating our understanding of miRNA functions in brain. We demonstrate the utility of this map for exploring clinically relevant miRNA binding sites that may facilitate the translation of genetic studies of complex neuropsychiatric diseases into therapeutics.

show abstract

Section: Resultsmentioning

confidence: 99%

Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain

Boudreau

Jiang

Gilmore

et al. 2014

Neuron

195

207

View full text Add to dashboard Cite

show abstract

“…The disease was confirmed in all the patients by molecular analysis. Mutations of patient 4-32 were described previously (16). Those with cardiac failure, a history of hematopoietic stem cell transplantation or orthopedic surgery, and those on nocturnal respiratory support were excluded from this study.…”

Section: Methodsmentioning

confidence: 99%

Impact of Enzyme Replacement Therapy on Linear Growth in Korean Patients with Mucopolysaccharidosis Type II (Hunter Syndrome)

et al. 2014

View full text Add to dashboard Cite

Hunter syndrome (or mucopolysaccharidosis type II [MPS II]) arises because of a deficiency in the lysosomal enzyme iduronate-2-sulfatase. Short stature is a prominent and consistent feature in MPS II. Enzyme replacement therapy (ERT) with idursulfase (Elaprase®) or idursulfase beta (Hunterase®) have been developed for these patients. The effect of ERT on the growth of Korean patients with Hunter syndrome was evaluated at a single center. This study comprised 32 patients, who had received ERT for at least 2 yr; they were divided into three groups according to their ages at the start of ERT: group 1 (<6 yr, n=14), group 2 (6-10 yr, n=11), and group 3 (10-20 yr, n=7). The patients showed marked growth retardation as they got older. ERT may have less effect on the growth of patients with the severe form of Hunter syndrome. The height z-scores in groups 2 and 3 revealed a significant change (the estimated slopes before and after the treatment were -0.047 and -0.007, respectively: difference in the slope, 0.04; P<0.001). Growth in response to ERT could be an important treatment outcome or an endpoint for future studies.Graphical Abstract

show abstract

“…Mutations in the IDS gene located at Xq28 are responsible for MPS II [2-5]. Affected patients show a progressive accumulation of GAG in the lysosomes of many organs and tissues, which contribute to the clinical manifestations of MPS II.…”

Section: Introductionmentioning

confidence: 99%

Phase I/II clinical trial of enzyme replacement therapy with idursulfase beta in patients with mucopolysaccharidosis II (Hunter Syndrome)

Sohn

Cho

Park

et al. 2013

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundMucopolysaccharidosis II (MPS II, Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by the deficiency of iduronate-2-sulfatase (IDS). In affected patients, glycosaminoglycan (GAG) accumulates in the lysosomes of many organs and tissues contributing to the pathology associated with MPS II. The objective of this phase I/II clinical study was to evaluate the efficacy and safety of recombinant human iduronate-2-sulfatase (idursulfase beta, Hunterase®) in the treatment of MPS II.MethodsThirty-one MPS II patients between 6 and 35 years of age were enrolled in a randomized, single-blinded, active comparator-controlled phase I/II trial for 24 weeks. Patients were randomized to active comparator infusions (N=11), 0.5 mg/kg idursulfase beta infusions (N=10), or 1.0 mg/kg idursulfase beta infusions (N=10). The primary efficacy variable was the level of urinary GAG excretion. The secondary variables were changes in the distance walked in 6 minutes (6-minute walk test, 6MWT), echocardiographic findings, pulmonary function tests, and joint mobility.ResultsPatients in all three groups exhibited reduction in urine GAG and this reduced GAG level was maintained for 24 weeks. Urine GAG was also significantly reduced in the 0.5 mg/kg and 1.0 mg/kg idursulfase beta groups when compared to the active comparator group (P = 0.043, 0.002, respectively). Changes in 6MWT were significantly greater in the 0.5 mg/kg and 1.0 mg/kg idursulfase groups than in the active comparator group (p= 0.003, 0.015, respectively). Both idursulfase beta infusions were generally safe and well tolerated, and elicited no serious adverse drug reactions. The most frequent adverse events were urticaria and skin rash, which were easily controlled with administration of antihistamines.ConclusionsThis study indicates that idursulfase beta generates clinically significant reduction of urinary GAG, improvements in endurance as measured by 6MWT, and it has an acceptable safety profile for the treatment of MPS II.Trial registrationClinicalTrials.gov: NCT01301898

show abstract

Identification of 11 novel mutations in 49 Korean patients with mucopolysaccharidosis type II

Cited by 26 publications

References 28 publications

Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain

Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain

Impact of Enzyme Replacement Therapy on Linear Growth in Korean Patients with Mucopolysaccharidosis Type II (Hunter Syndrome)

Phase I/II clinical trial of enzyme replacement therapy with idursulfase beta in patients with mucopolysaccharidosis II (Hunter Syndrome)

Contact Info

Product

Resources

About