Preimplantation genetic testing and birth defect prevention of hereditary sensory and autonomic neuropathy Ⅳ caused by novel NTRK1 mutation
10.3760/cma.j.cn101441-20201218-00678
- VernacularTitle:NTRK1基因新发突变致遗传性感觉和自主神经病4型的遗传学分析及出生缺陷阻断研究
- Author:
Fei SONG
1
;
Dawei CHEN
1
;
Ping ZHOU
1
;
Zhaolian WEI
1
;
Yunxia CAO
1
Author Information
1. 安徽医科大学第一附属医院妇产科，合肥 230022
- Publication Type:Journal Article
- Keywords:
Hereditary sensory and autonomic neuropathy Ⅳ;
Congenital insensitivity to pain with anhidrosis;
NTRK1 gene;
Preimplantaion genetic testing
- From:
Chinese Journal of Reproduction and Contraception
2021;41(7):650-654
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the application of next generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping of preimplantaion genetic testing for monogenic (PGT-M) in the prevention of hereditary sensory and autonomic neuropathy Ⅳ (HSAN Ⅳ).Methods:A Chinese family of HSAN Ⅳ was enrolled in this study. NGS and Sanger sequencing were combined to conduct mutational analysis of NTRK1 gene. Functional evaluation of mutation was performed through the cloning of expression construct. After whole genome amplification of biopsied trophectoderm cells, some high-frequency SNP markers were selected for NGS-based haplotyping, including SNPs located upstream and downstream of NTRK1 target region. Results:Two compound heterozygous mutations of the NTRK1 gene, the previously reported mutation c.850+1G>A and the novel frameshift mutation （c.963delG；p.Val321-Valfs*149）, were identified in the proband, inherited from maternal and paternal sides, respectively. The novel frameshift mutation created a new reading frame, leading to dysfunctional and truncated protein. According to the PGT-M results, one of the blastocysts, inherited the maternal pathogenic allele and the paternal normal allele, was thawed and transferred. While the other blastocyst inherited both pathogenic allele. Unfortunately, there was no subsequent pregnancy. Conclusion:This is the first report of preimplantation genetic testing of NTRK1 gene mutations in China. The novel frameshift mutation c.963delG expands the gene mutation spectrum of HSAN Ⅳ. NGS-based SNP haplotyping applied in PGT-M provides an effective way to prevent birth defects of single-gene inherited diseases.
