Case report: identification of one frameshift variant and two in cis non-canonical splice variants of NEB gene in prenatal arthrogryposis

Yuefang Liu; Juan Xu; Qiaoyi Lv; Zhe Liang; Lingling Li; Qiong Pan

doi:10.3389/fgene.2023.1220170

Case report: identification of one frameshift variant and two in cis non-canonical splice variants of NEB gene in prenatal arthrogryposis

Front Genet. 2023 Aug 31:14:1220170. doi: 10.3389/fgene.2023.1220170. eCollection 2023.

Authors

Yuefang Liu¹, Juan Xu², Qiaoyi Lv³, Zhe Liang¹, Lingling Li⁴, Qiong Pan¹

Affiliations

¹ Genetic and Prenatal Diagnosis Center, Huai'an Maternity and Child Clinical College of Xuzhou Medical University, Huai'an, China.
² Clinical Medical College, Yangzhou University, Yangzhou, China.
³ School of Medicine, Jiangsu University, Zhenjiang, China.
⁴ Family Planning Department, Huai'an Maternity and Child Clinical College of Xuzhou Medical University, Huai'an, China.

Abstract

NEB mutation is associated with congenital nemaline myopathies. Here, we report a family with recurrent prenatal arthrogryposis. Trio whole exome sequencing (WES) disclosed three novel NEB (NM_001271208.2) variants including one paternal frameshift c.19049_19050delCA (p.Thr6350Argfs*14) and two double maternal variants in cis c. [24871G>T;24871-10C>G] (p. [Val8291Phe;?]). They are evaluated as "likely pathogenic (LP)", "variant of uncertain of significance (VUS)", and "VUS", respectively. After further prediction, the c.24871G>T, c.24871-10C>G, and c.[24871G>T;24871-10C>G] were respectively genetically engineered into the three plasmids. Compared with their wild-type counterparts, the three plasmids all produced truncated transcripts, and also a significant proportion of the full-length transcripts, which allowed us to reclassify NEB c.24871G>T and c.24871-10C>G variants as LP. As far as we know, this is the first case carrying NEB allele-specific function of partial loss. This result helped the couple make informed reproductive choices and opt for assisted reproduction for future pregnancies. This study also increased awareness to the phenotype of prenatal nemaline myopathy and expanded the variant spectrum of NEB.

Keywords: NEB; case report; minigene; nemaline myopathies; non-canonical splice variant.

Publication types

Case Reports

Grants and funding

This work was granted by the Maternal and Child Health project of Jiangsu Province (Nos F201714 and F201707), Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy (XZSYSKF2020024), and the Huai’an Natural Science Research Program (HAB202217).