Methylation epigenetic analysis of a pedigree affected with Fragile X syndrome based on Nanopore long-read sequencing
10.3760/cma.j.cn511374-20230910-00123
- VernacularTitle:基于Nanopore的长读长测序对脆性X综合征一个家系的甲基化表观遗传学分析
- Author:
Conghui WANG
1
;
Panlai SHI
;
Li′na LIU
;
Xuechao ZHAO
;
Xiangdong KONG
Author Information
1. 郑州大学第一附属医院遗传与产前诊断中心，郑州 450052
- Keywords:
Long-read sequencing;
Fragile X syndrome;
FMR1 gene;
Methylation;
Dynamic mutation;
X chromosome inactivation
- From:
Chinese Journal of Medical Genetics
2024;41(11):1290-1295
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic basis for a Chinese pedigree affected with Fragile X syndrome (FXS) through Nanopore long-read sequencing.Methods:A FXS pedigree who had undergone genetic counseling at the First Affiliated Hospital of Zhengzhou University in April 2023 was selected as the study subject. Nanopore long-read sequencing, triplet-repeat primed PCR (TP-PCR), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and trinucleotide polymorphism genotyping of androgen receptor (AR) gene were used to analyze the FMR1 CGG repeat number, methylation, and X chromosome inactivation of the pedigree members. This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No. KS-2018-KY-36). Results:Full mutation and CpG island hypermethylation were detected in the proband. The elder sister of the proband had full mutation of the FMR1 gene on one X chromosome and hypermethylation of CpG island, while the FMR1 gene on the other X chromosome was normal. FMR1 premutation was detected in the proband′s mother. Conclusion:Nanopore long-read sequencing can simultaneously detect the dynamic mutation and methylation status of the FMR1 gene on the two X chromosomes of females, which has important value for the diagnosis of FXS in different genders.
