Magnetic Resonance Imaging in Mild Recessive RYR1 Gene-related Congenital Myopathies: Genetic and Histopathological Correlation
GHT Ng, JJK Ip, SHS Chan, RSL Ho, WWM Lam
Hong Kong J Radiol 2017;20:53-8
DOI: 10.12809/hkjr1715394
Objective: To review and evaluate the pattern of muscle involvement evidenced on magnetic resonance imaging (MRI) in patients with mild recessive mutations in ryanodine receptor type 1 (RYR1) gene–related congenital myopathies, and to compare the consistency with those previously reported, and correlate with genetic and histological analysis.
Methods: The thigh and calf MRI (axial T1-weighted and short-tau inversion recovery / T2-weighted) of three Chinese patients who presented with early-onset congenital myopathy and were subsequently confirmed to have a heterozygous autosomal recessive RYR1 gene mutation were retrospectively reviewed by two paediatric radiologists. Pattern of muscle involvement was documented, with correlation of focused mutational genetic analysis and histological analysis of muscle biopsies.
Results: All three patients showed selective involvement of the thigh muscles with relative sparing of the rectus femoris, gracilis, semitendinosus and adductor longus, consistent with a previously reported pattern. A more diverse pattern was noted within calf muscles, although the soleus still showed a generally more severe degree of fat infiltration than the gastrocnemius. One muscle biopsy confirmed rod bodies on Gomori trichrome staining and nemaline rods on electron microscopy. Mutational analysis of the RYR1 gene revealed three novel mutations (c.1675dupA, c.10615delC, and c.11956dupG), and two known missense mutations (c.3523G>A, c.3800C>G). The missense mutation c.3523G>A (p.Glu1175Lys) was identified in two patients, suggesting that this variant is probably a hotspot mutation in the Chinese population.
Conclusion: With characteristic and consistent patterns of muscle involvement and fat infiltration, muscle MRI of the thigh and calf is useful in establishing the diagnosis of RYR1-related congenital mypopathy in a Chinese population, thereby guiding more focused mutational analysis and management.
Authors’ affiliations:
GHT Ng, JJK Ip, WWM Lam: Department of Radiology, Queen Mary Hospital, Pokfulam, Hong Kong
SHS Chan: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Pokfulam, Hong Kong
RSL Ho: Department of Pathology and Clinical Biochemistry, Queen Mary Hospital, Pokfulam, Hong Kong
中文摘要
輕度隱性RYR1基因相關的先天性肌病的磁力共振成像：基因及組織病理學
吳愷婷、葉精勤、陳凱珊、何肇倫、林慧文
目的：回顧和評估輕度隱性RYR1基因突變的相關先天性肌病患者的磁力共振成像（MRI）的表現，並與已經出版的文獻比較，及分析基因和組織病理學的相關性。
方法：兩名兒科放射科醫生回顧分析3名華裔患者的大腿和小腿MRI（橫斷面T1W和STIR / T2W圖像）肌肉病變模式。患者早期出現先天性肌病，後來證實有異合常染色體隱性RYR1基因突變。基因突變和與肌肉活檢組織學的相關性進行了分析。
結果：3名患者均顯示其大腿肌肉有不同程度的涉及，而股直肌、股薄肌、半腱肌和內收肌長肌影響相對較少。這些特點與以前報告一致。小腿肌肉有更多樣的表現，儘管比目魚肌比腓腸肌有更嚴重的脂肪滲透。一名患者的肌肉活檢在電子顯微鏡下確認有Gomori三色染色桿狀體的和肌纖維線形小體。RYR1基因的突變分析揭示三個新的突變（c.1675dupA，c.10615delC和c.11956dupG）和兩個已知的錯義突變（c.3523G> A，c.3800C> G）。兩名患者都有c.3523G> A（p.Glu1175Lys）的錯義突變，表明該變體可能是中國人群中的突變熱點。
結論：大腿和小腿肌肉的涉及模式有助建立中國人群中RYR1相關先天性輕度病變的診斷，從而指導基因突變分析和處理。