Analysis of pathogenic gene variant in two children with Treacher-Collins syndrome
10.3760/cma.j.cn511374-20210205-00114
- VernacularTitle:两例Treacher-Collins综合征1型患儿基因变异分析
- Author:
Jie WANG
1
;
Xiaoping JI
;
Lichun ZHANG
;
Ruiting XU
;
Yan HUANG
;
Yaxian LIU
;
Liqiong WU
;
Jin AN
;
Zhiyuan GUO
;
Xiaohua WANG
Author Information
1. 内蒙古自治区妇幼保健院遗传优生科，呼和浩特 010010
- Keywords:
Treacher-Collins syndrome;
TCOF1 gene;
Heterogeneity
- From:
Chinese Journal of Medical Genetics
2022;39(6):625-629
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical and genetic characteristics of two children with a clinical diagnosis of Treacher Collins syndrome (TCS).Methods:Whole-exome sequencing was used to screen potential variants in the two children. Confirmation of suspected variants was performed through Sanger sequencing , multiplex ligation dependent probe amplification and real-time PCR in probands and their parents.Results:A heterozygous deletion variant, c. 4357_4360delGAAA, was detected in case one, while was de novo and verified by Sanger sequencing. Thevariant was classified as pathogenic(PVS1 + PM2+ PM6)according to ACMG guideline. The heterozygous deletion of exon 1-7 was seen in the same gene in case 2, which MLPA verified as heterozygous deletion of exon 1-6. This deletion was inherited from the father with a normal phenotype, and the father’s TCOF1 gene was suspected to be chimeric heterozygous deletion of exon 1-6 verified by MLPA. Conclusion:The identified variants in the TCOF1 gene probably underlie the two cases of TCS. There was no apparent correlation between genotype and phenotype. In addition, it shows a high interfamilial variability ranging from normal to full presentation of TCS. Genetic detection provided clinical diagnosis and genetic counselling for TCS patients .
