Clinical characteristics and genetic analysis of two children with X-linked Centronuclear myopathy due to variants of MTM1 gene

Abstract

To explore the clinical and genetic characteristics of two newborns with Central nuclear myopathy (CNM). Two newborns with CNM diagnosed clinically at Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology in April 2019 and November 2021 were selected as the study subjects, and their clinical data was collected. Both newborns and their parents were subjected chromosomal karyotyping analysis and whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Pathogenicity of the candidate variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Patient 1 was a male neonate and Patient 2 was a 20-day-old male infant. Both newborns had featured difficulty in breathing and swallowing. WES revealed that both had harbored hemizygous variants of the MTM1 gene, which were verified by Sanger sequencing. Patient 1 had harbored a c.1261A>G variant. Based on the ACMG guidelines, it was rated as pathogenic (PVS1+PM2_Supporting+PP3). Patient 2 harbored a c.342delT variant, which was also rated as pathogenic (PVS1+PM2_Supporting+PP3). The c.1261A>G and c.342delT variants of the MTM1 gene probably underlay the pathogenesis of CNM in the two patients.