全外显子测序技术在危重症新生儿遗传病中的应用价值

目的 探讨全外显子组测序（WES）技术在危重新生儿遗传病中的应用价值。方法 选取于该院新生儿重症监护室治疗的66例疑似遗传病或诊断不明的危重新生儿为研究对象。收集患儿临床资料，采集患儿及其父母静脉血行WES检测，完成遗传病因诊断。结合患儿的临床表现寻找相关的致病基因变异。结果 66例疑似遗传病或诊断不明的危重新生儿中，男34例，女32例，其中通过WES检测出有基因变异14例（21%）；1例患儿经WES检测未见有基因变异，但因临床表现高度怀疑为色素失禁症，联合多重连接酶探针依赖扩增技术，检测到IKBKG基因4~10号外显子的杂合缺失变异。15例检测出基因变异的患儿中，致病性基因变异10例（67%）；可疑致病性基因变异1例（7%）；基因变异意义未明4例（27%）。15例患儿中有13例行染色体检查，只有1例染色体异常。结论 染色体检查不能作为遗传病的确诊手段，WES检测技术是寻找疑似或诊断不明的危重新生儿遗传病的重要工具，然而WES技术有一定的局限性，可联合其他测序方法进行检测。

Application value of whole exome sequencing in critically ill neonates with inherited diseases

Objective To study the application value of whole exome sequencing (WES) in critically ill neonates with inherited diseases. Methods A total of 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis who were admitted to the neonatal intensive care unit were enrolled as subjects. The clinical data of the neonates were collected, and venous blood samples were collected from the neonates and their parents for WES. The clinical manifestations of the neonates were observed to search for related pathogenic gene mutations. Results Among the 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis (34 boys and 32 girls), 14 (21%) were found to have gene mutations by WES. One neonate had no gene mutation detected by WES but was highly suspected of pigment incontinence based on clinical manifestations, and multiplex ligation-dependent probe amplification detected a heterozygous deletion mutation in exons 4-10 of the IKBKG gene. Among the 15 neonates with gene mutations, 10 (67%) had pathogenic gene mutation, 1 (7%) was suspected of pathogenic gene mutation, and 4 (27%) had gene mutations with unknown significance. Among the 15 neonates, 13 underwent chromosome examination, and only 1 neonate was found to have chromosome abnormality. Conclusions Chromosome examination cannot be used as a diagnostic method for inherited diseases, and WES detection technology is an important tool to find inherited diseases in critically ill neonates with suspected inherited diseases or unclear clinical diagnosis; however WES technology has some limitation and it is thus necessary to combine with other sequencing methods to achieve an early diagnosis.