The pathogenic gene research in Chinese nonsyndromic craniosynostosis
10.3760/cma.j.cn114453-20210426-00186
- VernacularTitle:中国人群非综合征型颅缝早闭的致病基因研究
- Author:
Yingzhi WU
1
;
Jieyi CHEN
;
Meifang PENG
;
Sijia WANG
;
Xiongzheng MU
Author Information
1. 复旦大学附属华山医院整形外科，上海 200040
- Keywords:
Craniosynostosis;
Next generation sequencing;
Pathogenic gene;
Chinese population
- From:
Chinese Journal of Plastic Surgery
2022;38(6):609-613
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the common pathogenic gene mutation in non-syndromic craniosynostosis in Chinese population.Methods:Patients with non-syndromic craniosynostosis were recruited in Huashan Hospital Affiliated to Fudan University from March 2018 to December 2020. A clinical questionnaire was designed to collect the general information of the patients. The gene panel was designed by entering the keywords craniosynostosis and gene panel in PubMed, extracting all relevant literature from January 1995 to May 2017. The gene library was sequenced on the Illumina HiSeq X platform, and bioinformatic analysis and pathogenic analysis were performed.Results:A total of 237 literatures were reviewed in the PubMed and Ovid databases, and the total sample was 3375 patients, of which 1822 cases (54%) were detected with corresponding mutations, involving 21 pathogenic genes. Based on the mutation detection rate of not less than 0.4%, 12 genes were selected in the gene panel: FGFR2, TWIST1, FGFR3, EFNB1, FGFR1, SKI, POR, RAB23, TCF12, MSX2, SMAD3 and ERF. A total of 109 patients with non-syndromic craniosynostosis were recruited in this study, including 62 males and 47 females; the average age was 2.1 years old. All participants denied family history. The average age at childbearing of father was 28.3 years old and of mother was 26.7 years old. 14 different pathogenic/ probable pathogenic mutation loci were found in the gene sequences of 19 patients. The mutation rate was 17.4%. The 14 mutation varients were distributed in 5 genes (FGFR2, TWIST1 , TCF12, EFNB1 , and FGFR3) . The 14 mutations can be classified into 5 missense mutations, 3 nonsense mutations, 1 splice mutation, 1 frameshift mutation and 4 in-frame deletion mutations, 11 of which have not been reported. These 11 novel mutations were mainly concentrated in two genes, TWIST1 and TCF12. The mutation types included: 3 loss-of-function, 4 frameshift deletions, 3 missense mutations, and 1 frameshift insertion, of which 7 were de novo mutation.Conclusions:TWIST1 and TCF12 are common pathogenic genes in Chinese patients with non-syndromic craniosynostosis.
