title: Clinical and Genetic Characteristics of Romanian Patients with Mucopolysaccharidosis Type II.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy, 68, Motilor street, 400370, Cluj-Napoca, Romania. calkhuzouz@umfcluj.ro.
authors.forename: Camelia
authors.initials: C
authors.lastname: Alkhzouz
authors.affiliation: 1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy, 68, Motilor street, 400370, Cluj-Napoca, Romania.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lazea
authors.affiliation: 1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy, 68, Motilor street, 400370, Cluj-Napoca, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Bucerzan
authors.affiliation: 1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy, 68, Motilor street, 400370, Cluj-Napoca, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Nascu
authors.affiliation: 1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy, 68, Motilor street, 400370, Cluj-Napoca, Romania.
authors.forename: Eva
authors.initials: E
authors.lastname: Kiss
authors.affiliation: 1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy, 68, Motilor street, 400370, Cluj-Napoca, Romania.
authors.forename: Carmencita Lucia
authors.initials: CL
authors.lastname: Denes
authors.affiliation: 1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy, 68, Motilor street, 400370, Cluj-Napoca, Romania.
authors.forename: Paula
authors.initials: P
authors.lastname: Grigorescu-Sido
keywords: Hunter disease; Mucopolysaccharidosis type II; Romania