Department of Cardiology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital, Zhengzhou, Henan, China.
Henan Children's Neurodevelopment Engineering Research Center, Henan Provincial Clinical Research Center for Pediatric Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital, Zhengzhou, China.
Mol Genet Genomic Med. 2024 Apr;12(4):e2432. doi: 10.1002/mgg3.2432.
To analyze the clinical and genetic characteristics of a patient with Polyglucosan body myopathy 1 (PGBM1) caused by a novel compound heterozygous variant in the RBCK1 gene.
The clinical data of the patient were collected, next-generation sequencing technology was used to determine the exome sequence of the patient, and the suspected pathogenic locus was verified by Sanger sequencing.
Through whole-exome sequencing, we found that there were c.919G>T; p. (Glu307*) and c.723_730dup; p. (Glu244fs) variants of the RBCK1 gene in the patient, inherited from his parents, constituting a compound heterozygous variation. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), the two variants were rated as pathogenic, but there were no comparable cases. Previous literature reported 24 patients with RBCK1 gene variants, involving a total of 20 myocardial and 18 skeletal muscle cases.
The patient was twice diagnosed with cardiac insufficiency, neglecting the usual manifestations of muscle weakness, resulting in misdiagnosis. Later, novel variants in the RBCK1 gene were discovered through whole-exome sequencing, and symptomatic treatment was given after diagnosis. The importance of whole-exome sequencing technology in disease diagnosis and genetic counseling was emphasized.
分析 1 例 RBCK1 基因复合杂合变异所致聚己糖体肌病 1 型（PGBM1）患者的临床和遗传特征。
收集患者的临床资料，采用下一代测序技术对患者进行外显子组测序，并通过 Sanger 测序验证可疑致病基因座。
通过全外显子组测序，我们发现患者存在 RBCK1 基因的 c.919G>T;p.(Glu307*)和 c.723_730dup;p.(Glu244fs)变异，来源于父母，构成复合杂合变异。根据美国医学遗传学与基因组学学院（ACMG）的指南，这两个变异被评为致病性变异，但没有可比病例。先前的文献报道了 24 例 RBCK1 基因突变患者，共涉及 20 例心肌和 18 例骨骼肌病例。
患者两次被诊断为心功能不全，忽略了肌肉无力的常见表现，导致误诊。后来，通过全外显子组测序发现了新的 RBCK1 基因突变，并在诊断后进行了对症治疗。强调了全外显子组测序技术在疾病诊断和遗传咨询中的重要性。
