{
    "abstract": "Prenatal whole exome sequencing (WES) is becoming an increasingly used diagnostic tool for fetuses with structural anomalies. However, the identification of variants of uncertain significance (VUS) in clinically relevant genes can significantly complicate prenatal diagnosis and genetic counseling.\nA fetus conceived through in vitro fertilization at the third attempt presented with polydactyly and molar tooth sign at 24\u2009+\u20096 weeks of gestation. Trio-based WES was performed on both parents and the affected fetus, revealing a pair of compound heterozygous CPLANE1 variants (c.4646\u00a0A\u2009>\u2009T/p.Glu1549Val and c.1233\u00a0C\u2009>\u2009A/p.Tyr411*) potentially associated with Joubert syndrome. According to the ACMG guidelines, one of the biallelic variants was classified as VUS, and the other as pathogenic. However, these variants had no allele frequencies in the general population. The p.Tyr411* variant was classified as deleterious, while the p.Glu1549Val variant was located in highly conserved residues, was predicted to be damaging by in silico tools, and altered hydrogen bonding. Furthermore, CPLANE1 expression was highest in the brain during the embryonic and fetal stages. These findings provide additional support for the association between CPLANE1 variants in this fetus and Joubert syndrome. Thus, the most likely diagnosis was Joubert syndrome, and after careful consideration, the couple decided to terminate the pregnancy.\nThe expression patterns of CPLANE1 and the molecular effects of the variants may provide further evidence supporting the potential for prenatal diagnosis of Joubert syndrome in the case of biallelic VUS and pathogenic variant. This study suggests that molecular insights may play a role in interpreting VUS in clinically relevant prenatal genes for prenatal diagnosis.",
    "authors": [
        {
            "affiliation": "Department of Pediatric Neurology, School of Medicine, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, Chengdu, China.\nInstitute of Electronic and Information Engineering of UESTC in Guangdong, Dongguan, Guangdong, China.",
            "firstname": "Si-Xiu",
            "initials": "SX",
            "lastname": "Li"
        },
        {
            "affiliation": "Institute of Electronic and Information Engineering of UESTC in Guangdong, Dongguan, Guangdong, China.",
            "firstname": "Leiting",
            "initials": "L",
            "lastname": "Chen"
        },
        {
            "affiliation": "Department of Radiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.",
            "firstname": "Chen",
            "initials": "C",
            "lastname": "Deng"
        },
        {
            "affiliation": "Department of Obstetrics, School of Medicine, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, Chengdu, China.",
            "firstname": "Dongmei",
            "initials": "D",
            "lastname": "Tang"
        },
        {
            "affiliation": "Department of Pediatric Neurology, School of Medicine, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, Chengdu, China.",
            "firstname": "Jing",
            "initials": "J",
            "lastname": "Zhang"
        },
        {
            "affiliation": "Department of Pediatric Neurology, School of Medicine, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, Chengdu, China.",
            "firstname": "Wen-Guang",
            "initials": "WG",
            "lastname": "Hu"
        },
        {
            "affiliation": "Department of Prenatal Diagnosis, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.",
            "firstname": "Yu",
            "initials": "Y",
            "lastname": "Hu"
        },
        {
            "affiliation": "Department of Radiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. 449535176@qq.com.",
            "firstname": "Hua",
            "initials": "H",
            "lastname": "Lai"
        },
        {
            "affiliation": "Department of Obstetrics, School of Medicine, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, Chengdu, China. yczar@126.com.",
            "firstname": "Xiao",
            "initials": "X",
            "lastname": "Yang"
        }
    ],
    "conclusions": "The expression patterns of CPLANE1 and the molecular effects of the variants may provide further evidence supporting the potential for prenatal diagnosis of Joubert syndrome in the case of biallelic VUS and pathogenic variant. This study suggests that molecular insights may play a role in interpreting VUS in clinically relevant prenatal genes for prenatal diagnosis.",
    "copyrights": "\u00a9 2024. The Author(s).",
    "doi": "10.1186/s12884-024-07052-3",
    "journal": "BMC pregnancy and childbirth",
    "keywords": [
        "CPLANE1 gene",
        "Gene expression",
        "Joubert syndrome",
        "Molecular effects",
        "Prenatal diagnosis",
        "Variants of uncertain significance"
    ],
    "methods": null,
    "publication_date": "2024-12-27",
    "pubmed_id": "39725884\n31911674\n24723551\n33540854\n38834294\n28654730\n26237491\n29962246\n31085342\n24178751\n31158925\n29955609\n27081551\n29605658\n33794348\n34675960\n35582950\n37880672\n25741868\n32461654\n35092359\n30359267",
    "results": null,
    "title": "Uncertain significance and molecular insights of CPLANE1 variants in prenatal diagnosis of Joubert syndrome: a case report.",
    "xml": "<Element 'PubmedArticle' at 0x788504c7ca90>"
}