Mutational Analysis of the α-L-lduronidase Gene in Three Egyptian Families: Identification of Three Novel Mutations and Five Novel Polymorphisms

摘要

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder that results from a deficiency in α-L-iduronidase (IDUA), which is involved in the degradation of dermatan and heparan sulfates. MPS I has three clinical phenotypes, ranging from the severe Hurler form to the milder Scheie phenotype. In this study, mutational analysis of the IDUA gene in three unrelated Egyptian families with Hurler phenotype was performed by sequencing the IDUA exons and exon-intron boundaries. Three novel mutations (c.854delC in exon 6, T141S in exon 4, and IVS2+6c＞t) and the previously reported G51D in exon 1 were detected. In addition, nine sequence variants, including five previously unreported polymorphisms (N73H, N297N, R363S, IVS10 (3025) g＞t, and IVS11 (3318) c＞a), were identified. This is the first report of IDUA mutations in Egyptian patients with MPS I. Our study showed a heterogeneous pattern of mutations and polymorphisms among Egyptian patients.