Identification of a novel splicing variant of IDS gene in a pedigree affected with type II glycosaminoglycan product storage disease.
10.3760/cma.j.issn.1003-9406.2020.07.003
- VernacularTitle:Ⅱ型粘多糖贮积症致病基因
IDS内含子中一个新的RNA剪切变异
- Author:
Hongqiang XIE
1
,
2
,
3
,
4
;
Lijuan WANG
;
Sexin HUANG
;
Jie LI
;
Yang ZOU
;
Peiwen XU
;
Ming GAO
;
Ranran KANG
;
Yuping NIU
;
Xiaowei LIU
;
Yuan GAO
Author Information
1. Center for Reproductive Medicine, Shandong University
2. National Research Center for Assisted Reproductive Technology and Reproductive Genetics
3. Key Laboratory for Reproductive Endocrinology of Ministry of Education, China
4. Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, Shandong 250001, China. gaoyuan@sduivf.com.
- Publication Type:Journal Article
- From:
Chinese Journal of Medical Genetics
2020;37(7):713-716
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze variant of IDS gene in a pedigree affected with mucopolysaccharidosis type II (MPS II).
METHODS:The proband was subjected to next generation sequencing and Sanger sequencing to identify potential variants. Suspected variant was analyzed by its co-segregation with the disease in the pedigree. Its impact on mRNA splicing was analyzed by using reverse transcription PCR (RT-PCR).
RESULTS:A hemizygous IVS1-3T>G variant was found in the IDS gene in the proband. RT-PCR results revealed two abnormal cDNA fragments of 600 bp and 300 bp. The 600 bp fragment had inserted 216 nucleotides at the 3' end of intron 1, while the 300 bp fragment had lost 109 nucleotides at the 5' end of exon 2, which resulted in two truncated proteins comprising 38 and 92 amino acids, respectively, instead of the normal product (550 amino acids). The proband and his mother were respectively hemizygous and heterozygous for the variant. The same variant was not found among 100 normal controls.
CONCLUSION:The IVS1-3T>G variant of the IDS gene probably underlies the MPS II in this pedigree by causing reduction or elimination of the IDS protein.
