A Childhood Onset Nemaline Myopathy Caused by Novel Compound Heterozygote Variants in the Nebulin Gene

Case Report

Austin J Clin Case Rep. 2023; 10(7): 1303.

A Childhood-Onset Nemaline Myopathy Caused by Novel Compound Heterozygote Variants in the Nebulin Gene

Jing Xu*; Jie Wu; Xiaowen Li; Wei Jiang; Chunyang wang

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, China

*Corresponding author: Jing Xu Department of Neurology, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. Email: jingxu01@tmu.edu.cn

Received: September 12, 2023 Accepted: October 07, 2023 Published: October 14, 2023

Abstract

Congenital myopathies are clinically and genetically heterogeneous disorders, which often remain genetically undiagnosed for many years. Here we present a 20-year-old patient showing gradually deteriorated proximal muscle weakness and rod-shaped structures found in muscle fibers was suspected of having nemaline myopathy. Whole-exome sequencing and subsequent Sanger sequence analysis for the patient revealed a pathogenic mutation in NEB gene c.21522+3 (IVS 144) A>G and c.23722 (exon 165) A>T. Based on genetic analyses, we identified two novel, compound- heterozygous variants in the NEB gene, which cause a childhood- onset nemaline myopathy.

Keywords: Congenital myopathy; Nemaline myopathy; NEB; Next Generation Sequencing

Introduction

Nemaline Myopathy (NM) is a hereditary muscle disorder with a wide range of severity. The most common clinical symptoms include early-onset muscle weakness of proximal limb, neck flexors, weakness of respiratory muscles [1]. NM was historically defined by the muscle biopsy finding of nemaline rods [2].

Mutations in 12 genes have been associated with NM. The most common mutations are NEB (encoding nebulin) [3,4] and ACTA1 (skeletal muscle a-actin) [5,6], other mutant genes including TPM2 (β-tropomyosin) [7], TPM3 (a-tropomyosin) [8,9], KBTBD13 (Kelch repeat and BTB domain-containing protein 13) [9], CFL2 (cofilin-2) [10], KLHL40 (Kelch-like family member 40, KLHL40) [11], KLHL41 (Kelch-like family member 41, KLHL41) [12], LMOD3 (leiomodin-3) [13], MYPN (myopalladin) [14], TNNT1 (troponin T1) [15,16] and TNNT3 (troponin T3) [17].

Homozygous or compound heterozygous mutation in the nebulin gene on chromosome 2q23 is responsible of NM [18]. NEB gene encodes nebulin, a giant cytoskeletal protein that plays a role in specifying and maintaining the length of actin thin filaments in striated muscle [19]. Here, we report a case of NM in a 20-year-old boy using next-generation sequencing.

Case Report

A 20-year-old male patient presented in the clinic complaining of a longstanding history of weakness since early childhood. He reported that he never gained the ability to run. Symptoms were progressive, so that he had difficulty in climbing stairs. He denied any history of muscle pain and stiffness. There was no history of diplopia, shortness of breath, or change in urine color. The weakness was not fluctuating and not associated with dysphagia or facial weakness. He has one sister and one brother, both of them died when they were infants with unknow cause. Both parents did not report neuromuscular symptoms and were normal upon clinical examination (Figure 1).