Abstract
Background: Mucolipidosis (ML) II and III alpha/beta are lysosomal disorders caused by mutations in the GNPTAB gene which encodes the alpha and beta subunits of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase. Method: To explore the clinical and molecular characteristics of the 20 ML II and III alpha/beta patients, clinical data was collected and GNPTAB gene was analyzed by nest PCR and direct Sanger-sequencing. The activity of several lysosomal enzymes was measured in the plasma. Results: Among the 20 ML II and III alpha/beta patients, 6 patients were classified as ML II and 14 as ML III alpha/beta. The main clinical manifestations were joint stiffness, skeletal deformity, mental retardation and short stature. Bone X-ray examination showed radiological changes. The plasma arylsulfatase A and hexosaminidase A enzyme activities increased significantly. Urinary glycosaminoglycan values were normal. We detected mutations in GNPTAB in 35 of 40 alleles (87.5%). Mutation c.2715 + 1G > A and c.2404 C > T (p.Gln802Ter) were the most prevalent variants, accounting for 14.3% and 11.4%, respectively. Five novel mutations c.3335 + 5G > A, c.1284 + 1G > A, c.571 + 4 A > G, c.1634_1635delAA (p.Lys545Serfs*16) and c.1582T > C(p.Cys528Arg) were identified. Conclusion: Our study expands the spectrum of GNPTAB gene in China. Mutation c.2715 + 1G > A was the most prevalent mutation in our study. The novel mutation c.1284 + 1G > A might be a severe mutation associated with ML II.