Mucopolysaccharidosis type IIIB mutations in Chinese patients: Identification of two novel NAGLU mutations and analysis of two cases involving prenatal diagnosis

摘要

Background: Mucopolysaccharidosis type IIIB (MPS IIIB) is a lysosomal storage disorder caused by over 130 mutations in NAGLU gene. However, there are not much mutations that have been reported in China. Here we studied five MPS IIIB patients from three unrelated Chinese families. Methods: Urine test and NAGLU activity assay were used to validate the patients' type of MPS. We performed DNA analyses by direct sequencing, PCR-DHPLC, and PCR-restriction enzyme techniques. In addition, prenatal gene diagnosis was performed to one couple with two pregnancies. Finally RT-PCR and bioinformatics analysis were used to identify mutations. Result: A total of six different mutations were found, including a novel deletion, c.867delC, and five missense mutations, c.1081T>C (p.W361R) (novel), c.700C>T (p.R234C), c.874G>A (p.G292R), c.1693C>T (p.R565W), and c.1694G>A (p.R565Q). Prenatal diagnosis revealed that the first fetus was a compound heterozygote carrying two mutations (p.R565W and p.R565Q), whereas the second fetus carried only p.R565Q mutation. Conclusions: Our research may enrich the mutation spectrum of the NAGLU gene in the Chinese population and help us further in understanding the pathogenesis of MPS IIIB.