The Correlation Study of Phenotype and Genotype of a Rare SEDT Family in South China
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2022.0307
- VernacularTitle:中国南方一罕见迟发性脊椎骨骺发育不良大家系的表型和基因型的相关性研究
- Author:
Ying HUANG
1
;
Jie XIE
1
;
Shi-yao ZHENG
2
;
Jia TANG
3
;
Yi-bin GUO
1
Author Information
1. Department of Medical Genetics， Zhongshan School of Medicine， Sun Yat-sen University， Guangzhou 510080， China
2. Department of Medical Genetics， School of Medicine， Sun Yat-sen University， Shenzhen 518107， China
3. Guangdong Provincial Reproductive Science Institute， Guangzhou 510600， China
- Publication Type:Journal Article
- Keywords:
SEDT;
TRAPPC2 gene;
novel mutation;
identification
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2022;43(3):392-399
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo reveal the molecular pathogenesis of a family with hereditary dwarfism and the correlation between phenotype and genotype， so as to lay a foundation for prenatal and preimplantation gene diagnosis in the future. MethodsOn the basis of preliminary clinical diagnosis and pedigree analysis， the DNA samples of the proband and his family core members were sequenced by next generation sequencing. The candidate genes were identified by bioinformatics analysis. After the candidate genes and their novel variants were identified， the pathogenicity of the novel variants was identified by PCR， Sanger sequencing， RT-PCR， q-PCR and other methods. ResultsThrough whole exon sequencing， Sanger sequencing and bioinformatics analysis， it was confirmed that TRAPPC2 gene and its c.94 del G mutation were the most likely pathogenic mutations in the disease， and the possibility of IVS as （-1） del G was ruled out by RT-PCR. Through q-PCR detection， it was confirmed that the TRAPPC2 gene expression of patients and carriers was significantly lower than that of normal people （P＜0.01）， and the advanced structure prediction analysis of protein showed that there was a significant difference in the spatial structure of normal protein and mutant protein. According to the criteria of ACMG guidelines， it was identified as pathogenic mutation. ConclusionsThe disease of the proband is delayed spondyloepiphyseal dysplasia tarda （SEDT） of XR， and the c.94 del G， p.D32T， fxX6 of TRAPPC2 is a novel pathogenic mutation that has not been reported， which is the internal cause of the disease， and there is a significant correlation between genotype and phenotype. This study has further enriched the mutation spectrum of TRAPPC2 gene and laid a good foundation for future eugenics and early disease prevention.
