Abstract：
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).
CONCLUSIONS: 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.
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).
CONCLUSIONS: 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.
摘要：
目的：探讨Joubert综合征胎儿的临床特点及遗传基础。
方法：选择2021年2月26日在苏州市立医院就诊的孕妇作为研究对象。胎儿和她的父母进行了全外显子组测序（WES），和候选变体通过Sanger测序进行验证。还进行了她父亲的cDNA分析和她妹妹的RNA测序。
结果：发现胎儿带有TCTN1基因的复合杂合变体，即c.624G>A和c.96dupA（p。Glu33Argfs*49),从她的父亲和母亲那里继承下来，分别。她的姐姐还携带了父系c.624G>A变体，通过父亲的cDNA分析和姐姐的RNA测序，未检测到TCTN1基因的c.624G>A变体的mRNA转录本。根据美国医学遗传学和基因组学学院（ACMG）的指南，c.624G>A和c.96dupA变体均被分类为可能致病(PVS1+PM2_支持)。
结论：TCTN1基因的复合杂合变体可能是该胎儿发病机制的基础。上述发现还扩展了TCTN1基因的突变谱。
方法：选择2021年2月26日在苏州市立医院就诊的孕妇作为研究对象。胎儿和她的父母进行了全外显子组测序（WES），和候选变体通过Sanger测序进行验证。还进行了她父亲的cDNA分析和她妹妹的RNA测序。
结果：发现胎儿带有TCTN1基因的复合杂合变体，即c.624G>A和c.96dupA（p。Glu33Argfs*49),从她的父亲和母亲那里继承下来，分别。她的姐姐还携带了父系c.624G>A变体，通过父亲的cDNA分析和姐姐的RNA测序，未检测到TCTN1基因的c.624G>A变体的mRNA转录本。根据美国医学遗传学和基因组学学院（ACMG）的指南，c.624G>A和c.96dupA变体均被分类为可能致病(PVS1+PM2_支持)。
结论：TCTN1基因的复合杂合变体可能是该胎儿发病机制的基础。上述发现还扩展了TCTN1基因的突变谱。
