Abstract
Background: Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare X-linked disorder caused by deficiency of iduronate-2-sulfatase (I2S) enzyme, which leads to the accumulation of partially digested glycosaminoglycans (GAGs) in the lysosomes and induces multisystemic alteration (coarse facial features; skeletal dysplasia; hepatosplenomegaly; joint stiffness and contractures; heart, lung, vision, and hearing disability; profound neurological decline).
The purpose of this study is to present the clinical and genetic characteristics of Romanian patients with Hunter syndrome and the genotype–phenotype correlation.
Material and Methods: 15 unrelated patients, with MPS II ranging from mild (4 subjects) to severe phenotype (11 subjects) aged 2 to 20 years, were evaluated clinically, cognitive development, enzyme assay and molecular analysis.
Results: The molecular analysis of the 15 unrelated Romanian MPS II patients has identified 15 different mutations (2 major genetic defects (13%) and 13 minor genetic defects (87%)): microdeletions and point mutations (missense, nonsense), seven of them described for the first time—deletion encompassing 3 to exon 7; c823G>T, pD275Y; c.1600A>C (pN534H); c.102_10delAG (p.D5Cfs*11); c.448_471del (p.P150_P157del); c.421delA (p.I141Yfs*72); and c.419-1G>C. The major genetic defects were correlated with a severe course of disease.
Conclusion: This is the first study on the clinical and molecular characterization of the MPS II Romanian patients. This study supports the evidence of the mutational heterogeneity of the I2S gene as well as the difficulty to correlate genotype and phenotype in the patients with MPS II.
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Communicated by: Verena Peters
Appendices
Contributions of Individual Authors
Camelia Alkhzouz: study design, acquisition, analysis and interpretation of data, writing, and literature search
Cecilia Lazea: cardiac assessment of the patients and writing
Simona Bucerzan: acquisition, analysis, and interpretation of data
Ioana Nascu: acquisition, analysis, and interpretation of data
Eva Kiss: acquisition, analysis, and interpretation of data
Carmencita Lucia Denes: ultrasound assessment of the patients
Paula Grigorescu-Sido: study design; acquisition, analysis, and interpretation of data; and writing
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Camelia Alkhzouz
The Conflict of Interest Statements
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1.
Camelia Alkhzouz declares she has received speaker honorarium and travel and accommodation funding from Shire and Genzyme companies in the past 5 years.
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2.
Cecilia Lazea declares she has received travel and accommodation funding from Shire and Genzyme companies in the past 5 years.
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3.
Simona Bucerzan declares she has received travel and accommodation funding from Shire and Genzyme companies in the past 5 years.
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4.
Ioana Nascu declares she has received speaker honorarium and travel and accommodation funding from Shire and Genzyme companies in the past 5 years.
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5.
Eva Kiss has nothing to declare in the past 5 years.
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6.
Carmencita Lucia Denes.
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Paula Grigorescu-Sido has nothing to declare in the past 5 years.
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All the authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.
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The research study was approved by the hospital’s ethics committee.
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The written, informed consent was obtained from participants or their guardians prior to the genetic analysis. All genetic procedures were done in accordance with the ethical standards on human experimentation, of the hospital committee, and with the Helsinki Declaration of 1975, as revised in 2000.
Approval from the Institutional Committee for Care and Use of Laboratory Animals
This article does not contain any studies with animal subjects performed by any of the authors.
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Alkhzouz, C. et al. (2016). Clinical and Genetic Characteristics of Romanian Patients with Mucopolysaccharidosis Type II. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 33. JIMD Reports, vol 33. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_535
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DOI: https://doi.org/10.1007/8904_2016_535
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