Analysis of IDUA gene mutations in patients with mucopolysaccharidosis type i (MPS I)

MPS Type I resulted from a lack of ? -L- iduronidase enzyme encoded by IDUA gene. In this study, 15 patients clinically diagnosed with MPS Type I were screened using DNA sequence analysis to confirm of diagnosis at the molecular level and to identify disease-causing IDUA gene mutations. Ten of screened patients have 9 different IDUA gene mutations which of three ( p.M1L , p.A327P , p.P533L ) were missense, three ( p.Y64X , p.W402X , p.R628X ) were nonsense and three (c.494-1G > A, c.793-6C > G, c.793-5C > A) were splicing one. Seven of these mutations have already been reported in different populations and two are novel (c.793-6C > G, c.793-5C > A). Nine patients have carried the mutations as homozygous and one has it in compound heterozygous state. A putative deleterious effect of novel mutations on protein function has detected using two different computational programs. Even 5 patients have diagnosed with MPS Type I according to their clinical symptoms, absence of ?-L-iduronidase enzyme analyses results and having no disease causing IDUA gene mutations means these patients may have different MPS type. Meanwhile, 7 different previously described IDUA gene polymorphism (p.A8A, p.A20A, p.H33Q, p.R105Q, p.A314A, p.T410T and IVS5-8C > T) are determined in 3 of screened patients. Consequently, clinical diagnosis was verified at the molecular level using DNA sequence analysis and 10 of 15 patients with the diagnosis of MPS type I had different IDUA gene mutant alleles. Keywords: Mucopolysaccharidosis type I, Mutation screening, IDUA gene, α-L iduronidase enzyme