Neuromuscular Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Neurogenetics. 2024 Nov 26;26(1):9. doi: 10.1007/s10048-024-00787-3.
Congenital myasthenic syndromes (CMSs) are genetic disorders affecting motor function with variable symptoms. RAPSN-related CMS, caused by mutations in the RAPSN gene, leads to muscle weakness. Accurate diagnosis is essential for proper management. This study aims to analyze six Iranian families affected by RAPSN-CMS, focusing on clinical manifestations, genetic variants, treatment response, and outcomes. Clinical assessments, genetic analysis, and whole-exome sequencing were performed on the six families to identify RAPSN gene mutations. The study examined symptoms, disease severity, age of onset, treatment response, and outcomes. Treatment with pyridostigmine and salbutamol was given to assess its effectiveness. Three homozygous known variants in RAPSN gene were identified: c.491G > A in three families, c.264 C > A in two families, and c.-210 A > G in one family. Clinical assessments showed diversity in symptoms and treatment responses. Pyridostigmine and salbutamol treatment improved symptoms and quality of life. This study highlights the significance of molecular diagnosis for RAPSN-related congenital myasthenic syndromes (CMS) in Iran, marking the first comprehensive genetic analysis in the region. The identification of specific pathogenic variants underscores the unique genetic landscape of local patients. Furthermore, our long-term follow-up revealed variable treatment responses, emphasizing the need for personalized care strategies. The clinical variability among patients with identical mutations necessitates a multidisciplinary approach for effective management. By enhancing genetic awareness and refining follow-up methods, we aim to improve diagnosis accuracy and interventions, fostering better outcomes for affected families in the Iranian population.
先天性肌无力综合征 (CMSs) 是一种影响运动功能的遗传疾病，具有不同的症状。 RAPSN 相关 CMS 是由 RAPSN 基因突变引起的，导致肌肉无力。准确的诊断对于正确的管理至关重要。本研究旨在分析 6 个受 RAPSN-CMS 影响的伊朗家庭，重点关注临床表现、遗传变异、治疗反应和结果。对 6 个家庭进行了临床评估、基因分析和外显子组测序，以确定 RAPSN 基因突变。研究检查了症状、疾病严重程度、发病年龄、治疗反应和结果。给予吡啶斯的明和沙丁胺醇治疗，以评估其疗效。在 RAPSN 基因中发现了三个纯合的已知变异：三个家庭中存在 c.491G > A，两个家庭中存在 c.264C > A，一个家庭中存在 c.-210A > G。临床评估显示症状和治疗反应存在多样性。吡啶斯的明和沙丁胺醇治疗改善了症状和生活质量。本研究强调了分子诊断对伊朗 RAPSN 相关先天性肌无力综合征 (CMS) 的重要性，标志着该地区首次进行全面的基因分析。特定致病变异的鉴定突显了当地患者独特的遗传景观。此外，我们的长期随访揭示了不同的治疗反应，强调了需要制定个性化的护理策略。具有相同突变的患者之间的临床变异性需要采用多学科方法进行有效管理。通过提高遗传意识和改进随访方法，我们旨在提高诊断准确性和干预措施，为伊朗人群中受影响的家庭带来更好的结果。
