Xiang Jingjing, Zhang Lili, Ding Yang, Wang Ting
Center for Reproduction and Genetics, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu 215002, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Aug 10;41(8):957-961. doi: 10.3760/cma.j.cn511374-20230601-00331.
To explore the clinical characteristics and genetic basis for a fetus with Joubert syndrome.
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.
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).
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.
探讨一名患有Joubert综合征胎儿的临床特征和遗传基础。
选取2021年2月26日就诊于苏州市立医院的一名孕妇作为研究对象。对胎儿及其父母进行全外显子组测序（WES），并通过Sanger测序验证候选变异。同时对其父亲进行cDNA分析，对其姐姐进行RNA测序。
发现该胎儿携带TCTN1基因的复合杂合变异，即c.624G>A和c.96dupA（p.Glu33Argfs*49），分别遗传自其父亲和母亲。其姐姐也携带父亲的c.624G>A变异，通过对其父亲的cDNA分析和对其姐姐的RNA测序未检测到携带TCTN1基因c.624G>A变异的mRNA转录本。根据美国医学遗传学与基因组学学会（ACMG）的指南，c.624G>A和c.96dupA变异均被分类为可能致病（PVS1+PM2_Supporting）。
TCTN1基因的复合杂合变异可能是该胎儿发病机制的基础。上述发现也扩展了TCTN1基因的突变谱。
