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.