The Etiological Study of Three Hunter Syndrome Families in Southern China / 中山大学学报(医学科学版)

ObjectiveTo reveal the molecular pathogenesis of Hunter syndrome in three families in southern China and to clarify the correlation between phenotype and genotype， so as to lay a foundation for future prenatal or preimplantation genetic diagnosis. MethodsOn the basis of initial clinical diagnosis and pedigree analysis， qualitative detection of glycosaminoglycans in urine was performed first， and then anticoagulant blood samples were collected from the children and their relatives. DNA was extracted and the IDS gene sequence was analyzed by PCR and Sanger sequencing. Various methods such as RT-PCR and bioinformatics analysis were used to identify the pathogenicity of the new variants. ResultsThe urine test results of the patients in the three families were all strongly positive（++）. Probands were all male， with hemizygous mutations in IDS gene from their mothers， and the mutation sites were c.615_622delCATACAGT， c.847_848delGT and IVS7 ds+1 G>A， respectively. The cross-species conservation analysis showed that the amino acid of IDS gene mutation site was highly conserved during species evolution. Compared with the normal protein， mutant proteins exhibited significant differences in the predicted results of advanced structure. The variants identified in the three families were classified as pathogenic by ACMG criteria. ConclusionsThe three probands were diagnosed with Hunter syndrome. The c.615_622del（p.Il206Valfs*18）， c.847_848del（p.Val283Alafs*57） and IVS7 ds+1 G>A （p.G336Dfs*12） of IDS gene are all novel pathogenic mutations， which are the underlying causes of morbidity in children. This study has further enriched the mutation spectrum of IDS gene.

A Missense Mutation of IDS Gene in A Chinese Child with Mucopolysaccharidosis Type Ⅱ / 现代检验医学杂志

Objective To study the clinical characteristics and iduronate-2-sulfatase (IDS)gene mutation of one child patient with mucopolysaccharidosis type Ⅱ (MPS Ⅱ).Methods All the 9 exons of IDS gene were amplified by polymerase chain reaction (PCR)technlogy.The PCR products were screened by direct gene Sanger sequencing.Results A missense muta-tion (c.445T>C)on exon 4 was found after the analysis of the gene sequencing results of PCR products in this patient’s IDS gene.Thi smutation leaded to the 149th codon TCT encoded serine into a CCT encoding proline (p.Ser149Pro).Mean-while,the IDS gene in the parents were widetpye,so this was a de novo mutation.Conclusion The de novo mutation of IDS gene is the cause of our patient with?mucopolysaccharidosis,one novel mutation (p.Ser149Pro)was identified.