ABSTRACT
Objective:To explore the underlying genetic cause in two patients with mucopolysaccharidosis(MPS)using the whole-exome sequencing.Methods:Genomic DNA was extracted from the peripheral blood of two patients with MPS and their family members. Sanger sequencing and pedigree verification were performed on the pathogenic variants filtered by whole-exome sequencing. The function of the mutation sites was analyzed by bioinformatics software. The effect of the splice mutation on mRNA was further determined by reverse transcription-PCR(RT-PCR).Results:The proband 1 was a 25-year-old male, who carried compound heterozygous mutations of α-L-iduronidas(IDUA) gene: p. T179R and p. S633L, and was diagnosed as MPSⅠ. His mother and sister carried heterozygous p. T179R, while his father carried heterozygous p. S633L, consistent with the autosomal recessive inheritance pattern. The proband 2 was a 3-year-old male, who was hemizygous for IVS 6-8A>G of iduronate-2-sulfatase(IDS) gene. His mother and grandmother were heterozygous for this mutation, consistent with the X-linked recessive inheritance. The proband 2 was diagnosed as MPSⅡ. Sequencing of RT-PCR products showed that the IVS 6-8A>G mutation activated an upstream cryptic splice-site in intron 6, leading to 7 nucleotide insertion in exon 7, frameshift, and shorter peptide chain.Conclusion:In this study, IDUA p. T179R and p. S633L, and IDS IVS 6-8A>G mutations were found in two patients with MPS by whole exome sequencing, which further expanded the genotypic and phenotype spectrum of MPS.