Liu Fang, Jiang Yan, Gui Xin, Xiao Yangxue, Zhang Xiaohang, Zhang Xuemei, Gao Yali
Prenatal Diagnosis Center, Women and Children's Hospital Affiliated to Chongqing Medical University, Chongqing 400014, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2025 May 10;42(5):597-602. doi: 10.3760/cma.j.cn511374-20250401-00193.
To explore the genetic etiology of a Chinese pedigree with recurrent Joubert syndrome with negative results by whole-exome sequencing in the prior proband.
Chinese pedigree which opted elective abortion at the Women and Children's Hospital Affiliated to Chongqing Medical University in December 2024 was selected as the study subject. Whole-genome sequencing was carried out on fetal tissue after termination of pregnancy. Candidate variants were validated by Sanger sequencing and interpreted, while non-coding variant was analyzed using in silico prediction tools. RNA sequencing and cDNA sequencing were conducted on fetal brain tissue. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.2024YL045-02).
Both the fetus and the affected child were found to harbor compound heterozygous variants of the CEP290 gene, namely c.7341dup (p.Leu2448fs*8) (pathogenic, maternally inherited) and c.1523-408G>A (likely pathogenic, paternally inherited). Both in silico analysis and fetal brain RNA sequencing confirmed aberrant RNA splicing caused by the intronic variant.
This case has highlighted the value of combining whole-genome sequencing with RNA functional validation. Above results not only enriched the spectrum of CEP290 gene mutations but also underscored its diagnostic value in resolving complex prenatal cases, providing critical clues for the prenatal diagnosis and recurrence risk assessment in genetic counseling.
在先证者全外显子测序结果为阴性的情况下，探究一个患有复发性乔伯特综合征的中国家系的遗传病因。
选取2024年12月在重庆医科大学附属妇女儿童医院选择人工流产的中国家系作为研究对象。妊娠终止后对胎儿组织进行全基因组测序。通过桑格测序验证并解释候选变异，同时使用计算机预测工具分析非编码变异。对胎儿脑组织进行RNA测序和cDNA测序。本研究经医院医学伦理委员会批准（伦理编号：2024YL045 - 02）。
发现胎儿和患病儿童均携带CEP290基因的复合杂合变异，即c.7341dup（p.Leu2448fs*8）（致病，母系遗传）和c.1523 - 408G>A（可能致病，父系遗传）。计算机分析和胎儿脑RNA测序均证实内含子变异导致异常RNA剪接。
该病例突出了全基因组测序与RNA功能验证相结合的价值。上述结果不仅丰富了CEP290基因突变谱，还强调了其在解决复杂产前病例中的诊断价值，为遗传咨询中的产前诊断和复发风险评估提供了关键线索。
