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目的:探讨1例Joubert综合征(JS)胎儿的临床表型及遗传学病因。方法:选取2021年2月26日于苏州市立医院就诊的1例孕妇作为研究对象。应用全外显子组测序技术对孕妇夫妇及引产胎儿进行基因变异筛查，对疑似致病性变异进行Sanger测序验证，通过胎儿父亲的cDNA分析和姐姐的RNA转录组测序结果进一步探讨变异的致病机制。结果:全外显子组测序发现引产胎儿携带 TCTN1基因c.624G>A和c.96dupA(p.Glu33Argfs*49)复合杂合变异，该2个变异既往均未见报道。Sanger测序验证2个变异分别遗传自胎儿的父亲与母亲，胎儿的姐姐也携带父源c.624G>A杂合变异。胎儿父亲的cDNA分析和姐姐的RNA转录组测序均未检出包含c.624G>A的转录本。根据美国医学遗传学与基因组学学会(ACMG)相关指南，2个变异均评级为可能致病性(PVS1＋PM2_Supporting)。 结论:TCTN1基因c.624G>A和c.96dupA(p.Glu33Argfs*49)复合杂合变异可能是上述JS胎儿的遗传学病因，进一步丰富了 TCTN1基因的变异谱。

Objective:To explore the clinical characteristics and genetic basis for a fetus with Joubert syndrome.Methods:A pregnant woman who had visited Suzhou Municipal Hospital on February 26, 2021 was selected as the study subject. The fetus and her parents were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. cDNA analysis of her father and RNA sequencing of her sister were also carried out.Results:The fetus was found to harbor compound heterozygous variants of the TCTN1 gene, namely c. 624G>A and c. 96dupA (p.Glu33Argfs*49), which were inherited from her father and mother, respectively. Her sister also carried the paternal c. 624G>A variant, and mRNA transcripts with the c. 624G>A variant of the TCTN1 gene were not detected by cDNA analysis of her father and RNA sequencing of her sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 624G>A and c. 96dupA variants were both classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The compound heterozygous variants of the TCTN1 gene probably underlay the pathogenesis in this fetus. Above finding has also expanded the mutational spectrum of the TCTN1 gene.