Genetic analysis and reproductive intervention for 46 Chinese pedigrees affected with Hereditary multiple exostoses.
10.3760/cma.j.cn511374-20251224-00746
- Author:
Lilan SU
1
;
Xiao HU
;
Jing DAI
;
Zhengxing WAN
;
Duo YI
;
Shuangfei LI
;
Liang HU
;
Yueqiu TAN
;
Fei GONG
;
Ge LIN
;
Guangxiu LU
;
Qianjun ZHANG
;
Juan DU
;
Wenbin HE
Author Information
1. Guangxiu Hospital Affiliated to Hunan Normal University, Changsha, Hunan 410205, China. hewenbin@hunnu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Humans;
Female;
Male;
Pedigree;
Exostoses, Multiple Hereditary/diagnosis*;
N-Acetylglucosaminyltransferases/genetics*;
Adult;
Exostosin 1;
Asian People/genetics*;
Genetic Testing;
Exostosin 2;
Mutation;
China;
Prenatal Diagnosis;
Pregnancy;
Genetic Counseling;
Preimplantation Diagnosis;
Exome Sequencing;
East Asian People
- From:
Chinese Journal of Medical Genetics
2026;43(4):253-258
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention.
METHODS:Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010).
RESULTS:In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born.
CONCLUSION:This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
