title: [Mutation analysis and prenatal diagnosis of 2 cases with mucopolysaccharidosis type I].
abstract: OBJECTIVE
  Mucopolysaccharidosis type I (MPS I; MIM# 252800) is an autosomal recessive disease that results from the deficiency in the lysosomal enzyme α-L-iduronidase(IDUA). IDUA is one of the enzymes involved in degradation of glycosaminoglycans heparan sulphate and dermatan sulphate. The deficiency of IDUA leads to widespread accumulation of partially degraded mucopolysaccharides inside lysosomes, resulting in progressive cellular and multiorgan dysfunction. Up to now there is no definitely effective treatment for this disorder, therefore it is important to provide an accurate genetic diagnosis and prenatal diagnosis for the MPSI families. This study was conducted to detect IDUA gene mutation in patients with MPSIand make a definite diagnosis of homozygote or heterozygote and make first trimester prenatal diagnosis.
  
  
  METHODS
  The 2 male probands included in this study were diagnosed as MPSI patients in Peking Union Medical College Hospital, case 1 was 2 years old and case 2 was 5 years old. Genomic DNA was extracted from leucocytes in the 2 patients and 2 mothers' cultured amniocytes. IDUA gene DNA sequence was amplified by polymerase chain reaction (PCR) and the PCR products were sequenced directly. Novel mutations were analyzed in 100 normal chromosomes.
  
  
  RESULTS
  The genotype of case 1 was p.L238R/c.883InsC, while of case 2 was c.531InsT/p.L346R. The fetal case 1 did not inherit the same pathogenic mutations as proband 1, the activity of the IDUA in amniocytes was 9.0 nmol/(h·mg pr). The fetal case 2 inherited the same pathogenic mutations with the proband, the genotype of fetal 2 was c.531InsT/p.L346R, the activity of the IDUA in amniocytes was 0.5 nmol/(h·mg pr).
  
  
  CONCLUSIONS
  Of the 4 mutations found in 2 MPS I patients, p. L238R, c.883InsC, c.531InsT were novel. The fetal case 1 was diagnosed as normal fetus while the fetus 2 was diagnosed as affected. The results of the two kinds of prenatal diagnostic methods were correspondent with each other.
authors.affiliation: Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Xin-Ning
authors.initials: XN
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Shi
authors.forename: Zheng-Qing
authors.initials: ZQ
authors.lastname: Qiu
authors.forename: Feng-Xia
authors.initials: FX
authors.lastname: Yao
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Zhang
mesh_terms: D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007068:Iduronidase / Q000235:genetics*; D008297:Male; D008059:Mucopolysaccharidosis I / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D007068:Iduronidase