目的：总结先天性肌病患儿临床表现、实验室检查和基因突变特点，以期提高其诊断及为遗传咨询提供依据。方法：回顾性分析2020年1月至2023年10月南京医科大学附属儿童医院收治的经基因诊断确诊为先天性肌病的8例患儿的连续病例资料，经家长同意后进行基因检测并对检测结果进行遗传学分析及致病性预测。结果：共收集8例先天性肌病患儿。其中男3例、女5例，8例患儿起病年龄均≤3岁，且均存在运动发育落后。2例患儿存在认知发育落后；1例先天性髋关节脱位；2例足异常，分别表现为足下垂、双足扁平外翻；3例患儿有不同部位的肌肉萎缩。所有患儿均表现为不同程度的肌力减弱，他们的血清肌酸激酶均正常或轻度升高。所有患儿肌电图均提示肌源性损害。1例患儿完善肌肉活检提示为中央核型肌病。分子遗传学结果分析提示：RYR1基因突变3例，TNN、SPEG基因各2例，NEB基因1例。基因的突变类型以错义突变为主，剪切位点突变、移码突变相对少见。本研究发现了4种基因共12个突变位点，其中8个经ACMG评级为致病性不明的错义突变位点通过生物信息学软件进行蛋白质二级结构预测后发现RYR1 c.5339C>A(p.P1780H)、c.10442C>T(p.A3481V)位点与周围分子无氢键结合力，突变仅局限于个体小分子结构，RYR1 c.14021G>A(p.R4674Q)突变后破坏了氨基酸氢键结合力。RYR1 c.9122G>C(p.S3041T)、c.14640G>A(p.M4880I)位点突变均不影响氢键结合力。同一家系患儿携带的SPEG基因两处变异位点c.3588delC和c.3715+4C>T的致病性机制研究提示，c.3588delC位点突变后的SPEG蛋白较野生型形态及大小均发生了明显改变，可导致多个Ig-like及蛋白激酶结构域丢失。c.3715+4C>T导致SPEG基因剪切改变，提前形成终止密码：RYR1基因突变位点：c.14021G>A、c.9122G>C、c.5339C>A、c.14640G>A、c.10442C>T；TTN基因突变位点：c.95078C>A、c.105520C>T、c.59282A>G；NEB基因突变位点：c.18622C>G、c.7355A>G；SPEG基因突变位点：c.3715+4C>T、c.3588delC。结论:先天性肌病起病隐匿，临床表现差异较大，缺乏特异性。详细的病史询问、体格检查、分子遗传学检查，必要时的肌肉病理检查对诊断先天性肌病尤为重要。本研究总结先天性肌肉病的临床表现及分子遗传学特点，为提高该类疾病的诊治及遗传咨询等提供重要依据。

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