AUTHOR=Zhuang Jianlong , Wang Junyu , Luo Qi , Zeng Shuhong , Chen Yu’e , Jiang Yuying , Chen Xinying , Wang Yuanbai , Xie Yingjun , Wang Gaoxiong , Chen Chunnuan 

TITLE=Case Report: Novel compound heterozygous variants in CHRNA1 gene leading to lethal multiple pterygium syndrome: A case report

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.964098

DOI=10.3389/fgene.2022.964098

ISSN=1664-8021

ABSTRACT=Background: Lethal multiple pterygium syndrome (LMPS) is a rare autosomal-recessively inherited disorder typically manifested intrauterine growth retardation, multiple pterygia and flexion contractures. Our goal was to investigate genetics etiology in a fetus with recurrent lethal multiple pterygium syndrome using whole exome sequencing.
Case presentation: A Chinese family with a history of three adverse pregnancies was enrolled in this study. The previous three fetuses demonstrated similar ultrasonic phenotypes, including increased nuchal translucency, edema, fetal neck cystoma, reduced movement, joint contractures and other congenital features. The 2nd and 3rd pregnancies were available for genetic etiology diagnosis. None of chromosome abnormality and copy number variants was detected in both fetuses using fetal karyotype and chromosomal microarray analysis. Further whole exome sequencing (WES) revealed a novel mutation of c.1128delG (p.P377Lfs*10) compound with a novel c.505T>C (p.W169R) mutation in CHRNA1 gene in both fetuses, which would lead to LMPS and may be responsible for the clinical features in the fetuses and were inherited from the parents respectively by further parental verification.
Conclusion: In this study, two novel compound heterozygous mutations in CHRNA1 gene that leads to recurrent lethal multiple pterygium syndrome was first identified in a Chinese family. In addition, our study enriches the spectrum mutations of CHRNA1 gene that result in LMPS and further enhances the application value of prenatal WES technology in genetic etiology diagnosis of fetuses with ultrasound anomalies.