Diagnosis of fetal nemaline myopathy by whole-exome sequencing: case report and review of literature

Abstract

Objective: In this article we present a case of fetal nemaline myopathy (NM) diagnosed by whole-exome sequencing (WES) and confirmed by fetal muscular pathology, and we review the clinical, pathological, and genetic characteristics of congenital NM. Method: A pregnant woman with recurrent fetal hydrops and polyhydramnios was recommended to undergo WES before termination of pregnancy in order to find the etiology of these issues. After delivery, we obtained umbilical-cord blood and parental peripheral blood samples for WES. Fetal muscle was subjected to modified Gomori technique (MGT) and hematoxylin phosphotungstate (PTAH) staining for light microscope detection. Results: WES revealed two compound heterozygous mutations to fetal Kelch-like 40 (KLHL40), and pedigree-based Sanger sequencing showed that c.602G > A (p.Trp201*) was inherited from the mother and c.1516A > C (p.Thr506Pro) from the father. MGT and PTAH staining highlighted numerous nemaline rods under the light microscope. Conclusion: Fetal NM is a lethal genetic muscle disorder that is one etiology of fetal akinesia deformation sequence (FADS). Pathological and genetic testing are the current diagnostic methods for NM, but WES is a promising method for prenatal diagnosis of this disorder.

Keywords

• nemaline myopathy
• fetal akinesia
• gene
• pathology
• whole-exome sequencing