摘要目的:探讨1例出生后2 d死亡的肺泡毛细血管发育不良伴肺静脉错位(ACD/MPV)患儿的遗传学特征及其死亡原因。方法:选取2022年9月就诊于南通大学附属妇幼保健院的1例ACD/MPV患儿作为研究对象。采集患儿的临床资料。应用全外显子组测序(WES)技术对患儿皮肤组织进行基因检测，针对候选致病变异，进行Sanger测序家系验证。应用液滴数字PCR(ddPCR)技术检测该变异在患儿父亲不同胚层来源标本中的嵌合比例。结果:患儿出生后2 d因"低氧血症和呼吸窘迫"死亡。WES结果显示患儿携带 FOXF1基因c.433C>T杂合变异，既往未见报道。Sanger测序验证患儿存在该变异，母亲该位点为野生型，父亲外周血样中该位点可见微小变异峰。ddPCR提示其父亲精液中c.433C>T变异嵌合比例为27.18%，源于3个胚层的组织中该变异嵌合比例为11%~28%。 结论:本研究患儿携带的源自其嵌合变异父亲的 FOXF1基因c.433C>T杂合变异可能为导致该患儿死亡的遗传学病因。ddPCR为检测变异嵌合的有效手段。

abstractsObjective:To investigate the genetic characteristics and cause of death for an infant with alveolar capillary dysplasia and pulmonary vein misalignment (ACD/MPV).Methods:An infant with ACD/MPV diagnosed at the Affiliated Maternity and Child Health Care Hospital of Nantong University in September 2022 was selected as the study subject. Clinical data of the infant were collected. Whole exome sequencing (WES) was carried out to detect genetic variants in the skin tissue, and Sanger sequencing was performed for verifying the candidate variants in the parents. Droplet digital PCR (ddPCR) was used to determine the mosaicism ratio of the variant in different germ layer-derived samples from the father.Results:The infant had died within 2 days after birth due to hypoxemia and respiratory distress. WES revealed that she has harbored a c. 433C>T nonsense variant in exon 1 of the FOXF1 gene, which was unreported previously. Sanger sequencing has verified the variant in the infant, with her mother's locus being the wild-type and a minor variant peak noted in her father. ddPCR indicated that the mosaic ratio of the c. 433C>T variant in the father's sperm was 27.18%, with the mosaic ratios of the variant in tissues originating from the three germ layers ranging from 11% to 28%. Conclusion:The c. 433C>T variant derived from the paternal germline and somatic mosaicism of the FOXF1 gene had probably predisposed to the neonatal death of this infant. ddPCR is an effective method for detecting mosaic variants.