摘要本研究旨在分析一家系两例发育迟缓、乳酸酸中毒新生儿的临床特征及基因变异特点，探讨基因变异与临床特征的关系。回顾性分析2019年5月和2021年12月于重庆医科大学附属儿童医院新生儿科病房就诊的两例发育迟缓、乳酸酸中毒新生儿的临床特征；利用全外显子测序检测患儿基因变异；对BCS1L蛋白进行同源建模，分析模型蛋白的结构和功能改变；分析基因变异与临床表型的相关性。结果显示，该家系两例患儿的主要临床特征为线粒体呼吸链复合体Ⅲ缺陷症表现，包括早产、发育迟缓、呼吸衰竭、乳酸酸中毒、胆汁淤积、肝功能异常、肾小管病变、凝血功能异常、贫血、低血糖、肌张力低下和早期死亡。全外显子测序发现 BCS1L基因c.486_488delGGA（p.E163del）新型缺失变异和c.992C>T（p.T331I）新型错义变异，蛋白同源建模结构分析结果显示复合杂合变异对蛋白功能影响较大。综上， BCS1L基因新的变异位点c.992C>T（p.T331I）为“可能致病”变异，复合杂合变异与线粒体呼吸链复合体Ⅲ缺陷症疾病表型密切相关。

abstractsThis study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children′s Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486_488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.