Abstract：
OBJECTIVE: To explore the clinical and genetic characteristics of two newborns with Central nuclear myopathy (CNM).
METHODS: 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).
RESULTS: 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).
CONCLUSIONS: The c.1261A>G and c.342delT variants of the MTM1 gene probably underlay the pathogenesis of CNM in the two patients.
METHODS: 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).
RESULTS: 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).
CONCLUSIONS: The c.1261A>G and c.342delT variants of the MTM1 gene probably underlay the pathogenesis of CNM in the two patients.
摘要：
目的：探讨2例中枢神经性肌病(CNM)新生儿的临床和遗传特点。
方法：同济医学院附属武汉儿童医院临床诊断为CNM的2例新生儿，华中科技大学于2019年4月和2021年11月作为研究对象。并收集了他们的临床数据。对新生儿及其父母进行染色体核型分析和全外显子组测序（WES）。通过Sanger测序验证候选变体。基于美国医学遗传学和基因组学学院(ACMG)的指南评估候选变体的致病性。
结果：患者1为男性新生儿，患者2为20天大的男性婴儿。两个新生儿都有呼吸困难和吞咽困难。WES显示两者都含有MTM1基因的半合子变体，经Sanger测序验证。患者1具有c.1261A>G变体。根据ACMG指南,它被评为致病性(PVS1+PM2_支持+PP3)。患者2携带c.342delT变体，也被评为致病性(PVS1+PM2_支持+PP3)。
结论：MTM1基因的c.1261A>G和c.342delT变异可能是2例CNM发病机制的基础。
方法：同济医学院附属武汉儿童医院临床诊断为CNM的2例新生儿，华中科技大学于2019年4月和2021年11月作为研究对象。并收集了他们的临床数据。对新生儿及其父母进行染色体核型分析和全外显子组测序（WES）。通过Sanger测序验证候选变体。基于美国医学遗传学和基因组学学院(ACMG)的指南评估候选变体的致病性。
结果：患者1为男性新生儿，患者2为20天大的男性婴儿。两个新生儿都有呼吸困难和吞咽困难。WES显示两者都含有MTM1基因的半合子变体，经Sanger测序验证。患者1具有c.1261A>G变体。根据ACMG指南,它被评为致病性(PVS1+PM2_支持+PP3)。患者2携带c.342delT变体，也被评为致病性(PVS1+PM2_支持+PP3)。
结论：MTM1基因的c.1261A>G和c.342delT变异可能是2例CNM发病机制的基础。
