Two patients with congenital myasthenic syndrome caused by COLQ gene mutations and the consequent ColQ protein defect

Qiting Zhang; Qianqian Sha; Kai Qiao; Xiaoli Liu; Xiaohui Gong; Ailian Du

doi:10.1016/j.heliyon.2023.e13272

Two patients with congenital myasthenic syndrome caused by COLQ gene mutations and the consequent ColQ protein defect

Heliyon. 2023 Jan 26;9(2):e13272. doi: 10.1016/j.heliyon.2023.e13272. eCollection 2023 Feb.

Authors

Qiting Zhang¹, Qianqian Sha¹, Kai Qiao², Xiaoli Liu³, Xiaohui Gong⁴, Ailian Du¹

Affiliations

¹ Department of Neurology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China.
² Department of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
³ Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, 201406, China.
⁴ Department of Neonatology, Shanghai Children's Hospital, Shanghai, 200062, China.

Abstract

Objective: To report two cases of congenital myasthenic syndromes (CMS) in a Chinese family with mutations in the COLQ gene and to prove the consequence defect of the ColQ protein.

Method: Clinical characteristics of the two children from the same family were described. Next-generation sequencing (NGS) and sanger sequencing was performed on the proband and family members. The consequence of the mutation was predicted by 3D protein structure prediction using I-TASSER. The wild type and mutant were transfected to 293T cells, and ColQ protein was detected by Western Blot.

Results: The diagnosis of CMS was based on a symptom combination of fatigable muscle weakness, ptosis, scoliosis, and hypotonia, aggravation of muscle weakness after the neostigmine test, and a 46% decrement in repetitive nerve stimulation. A muscle biopsy was performed on the proband, revealing mild variation in the myofiber size. NGS data revealed two compound heterozygous mutations at c.173delC (p.Pro58Hisfs*22) and c.C706T (p.R236X) in the COLQ gene, where the former was a novel mutation. A 3D structure prediction showed two truncated ColQ proteins with 78aa and 235aa, respectively. The truncated ColQ protein was proved in 293T cells transfected with c.173delC or c.C706T mutants by Western Blot.

Conclusions: The mutations of c.173delC and c.C706T in the COLQ gene led to truncated ColQ protein and contributed to the pathogenesis of CMS in this Chinese family.

Keywords: 3D structure prediction; COLQ gene; Congenital myasthenic syndrome (CMS); Next-generation sequencing (NGS); Truncated protein.

Publication types

Case Reports