The Etiological Study of Three Hunter Syndrome Families in Southern China
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2023.0317
- VernacularTitle:中国南方三个Hunter综合征家系的病因学研究
- Author:
Shi-yao ZHENG
1
;
Jia TANG
2
;
Yang AI
2
;
Xiao-yun WU
2
;
Jie XIE
2
;
Ying HUANG
2
;
Yi-bin GUO
1
Author Information
1. Department of Medical Genetics， School of Medicine， Sun Yat-sen University， Shenzhen 518107， China
2. Department of Medical Genetics， Zhongshan School of Medicine， Sun Yat-sen University， Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
Hunter syndrome;
IDS gene;
iduronate-2-sulfatase;
novel mutation
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2023;44(3):490-496
- CountryChina
- Language:Chinese
-
Abstract:
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.
