BACKGROUND: Mucopolysaccharidosis (MPS) is induced by the absence or malfunctioning of lysosomal enzymes. MPS I and MPS II are similar in phenotypes but they are different in genotypes, which are caused by the deficiencies of alpha-L-iduronidase gene (IDUA) and iduronate 2-sulfatase gene (IDS) respectively. In this work, a 5-year-old Chinese young male with manifestations of MPS in a family with unaffected parents was described. METHODS: 12 kb of all the targeted exon sequences plus flanking sequences chromosomal DNA of IDS and IDUA genes from the proband and 20 other case-unrelated controls were captured and sequenced by using next-generation sequencing technology. RESULTS: One single-nucleotide deletion variant (c.1270delG) resulting in frameshift and premature truncation of I2S enzyme was detected, out of 20 controls, only in the proband, and which was further verified by Sanger sequencing. The proband's mother was also proved carrying c.1270delG by Sanger method but not for his father. CONCLUSIONS: The novel variant (c.1270delG) is a candidate disease-causing mutation predicted to affect the normal structure and function of the enzyme. Target sequence capture and next-generation sequencing technology can be effective for the gene testing of MPS II disorder.
BACKGROUND:Mucopolysaccharidosis (MPS) is induced by the absence or malfunctioning of lysosomal enzymes. MPS I and MPS II are similar in phenotypes but they are different in genotypes, which are caused by the deficiencies of alpha-L-iduronidase gene (IDUA) and iduronate 2-sulfatase gene (IDS) respectively. In this work, a 5-year-old Chinese young male with manifestations of MPS in a family with unaffected parents was described. METHODS: 12 kb of all the targeted exon sequences plus flanking sequences chromosomal DNA of IDS and IDUA genes from the proband and 20 other case-unrelated controls were captured and sequenced by using next-generation sequencing technology. RESULTS: One single-nucleotide deletion variant (c.1270delG) resulting in frameshift and premature truncation of I2S enzyme was detected, out of 20 controls, only in the proband, and which was further verified by Sanger sequencing. The proband's mother was also proved carrying c.1270delG by Sanger method but not for his father. CONCLUSIONS: The novel variant (c.1270delG) is a candidate disease-causing mutation predicted to affect the normal structure and function of the enzyme. Target sequence capture and next-generation sequencing technology can be effective for the gene testing of MPS II disorder.