Department of Medical Imaging Center, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
Medical Genetics Center, Jiangmen Maternity and Child health Care Hospital, Jiangmen, China.
J Clin Lab Anal. 2020 Feb;34(2):e23054. doi: 10.1002/jcla.23054. Epub 2019 Oct 18.
Centronuclear myopathy (CNM), a subtype of congenital myopathy (CM), is a group of clinical and genetically heterogeneous muscle disorders. Centronuclear myopathy is a kind of disease difficult to diagnose due to its genetic diversity. Since the discovery of the SPEG gene and disease-causing variants, only a few additional patients have been reported.
A radiograph test, ultrasonic test, and biochemical tests were applied to clinical diagnosis of CNM. We performed trio medical exome sequencing of the family and conservation analysis to identify variants.
We report a pair of severe CNM twins with the same novel homozygous SPEG variant c. 8710A>G (p.Thr2904Ala) identified by clinical trio medical exome sequencing of the family and conservation analysis. The twins showed clinical symptoms of facial weakness, hypotonia, arthrogryposis, strephenopodia, patent ductus arteriosus, and pulmonary arterial hypertension.
Our report expands the clinical and molecular repertoire of CNM and enriches the variant spectrum of the SPEG gene in the Chinese population and helps us further understand the pathogenesis of CNM.
核性肌病（CNM）是先天性肌病（CM）的一种亚型，是一组具有临床和遗传异质性的肌肉疾病。由于遗传多样性，核性肌病是一种难以诊断的疾病。自 SPEG 基因和致病变异的发现以来，仅报道了少数其他患者。
对 CNM 患者进行放射学检查、超声检查和生化检查进行临床诊断。我们对家系进行了三代人外显子组测序，并进行了保守性分析以鉴定变异。
我们报道了一对严重的 CNM 双胞胎，他们通过家系的三代人外显子组测序和保守性分析确定了相同的新型纯合 SPEG 变异 c.8710A>G（p.Thr2904Ala）。这对双胞胎表现出面肌无力、张力减退、关节挛缩、蹼状指、动脉导管未闭和肺动脉高压的临床症状。
我们的报告扩展了 CNM 的临床和分子谱，并丰富了中国人群中 SPEG 基因的变异谱，有助于我们进一步了解 CNM 的发病机制。
