{
    "abstract": "Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a rare inherited channelopathy, responsible for potentially lethal malignant arrhythmic episodes. Atypical non-juvenile form of CPVT may not mislead an alternative diagnosis of calcium release deficiency syndrome (CRDS).\nThe index case was a 58 years-old woman who experienced aborted sudden cardiac arrest. The initial complete diagnostic workup (including norepinephrine challenge) was completely negative. She was implanted with an entirely subcutaneous defibrillator. During her follow-up, she received an appropriate electrical shock (ventricular fibrillation) despite \u03b2-blocker treatment. Three sisters (46, 40 and 18 years-old) as well as 2 cousins, one paternal uncle and one paternal aunt had sudden cardiac deaths (SCD) without etiology in the family history. There were no additional reports of pregnancy loss, neonatal death, seizures or SCD among the family members. The genetic analysis in this proband revealed a missense pathogenic variant c.13823\u202fG>A, p.(Arg4608Gln) in the RYR2 gene, encoding the Ryanodine Receptor type 2. This c.13823\u202fG>A, p.(Arg4608Gln), variant in the RYR2 gene was supposed to be a potential disease-causing variant in CPVT. Unfortunately, before the end of the proband's genetic analysis, her 20 years-old daughter experienced SCD, whilst being implanted with an insertable cardiac monitor. Familial segregation analysis confirmed the four symptomatic sisters harbor also the same variant confirming the pathogenic role of this variant. We also identified 7 carriers who were clinically negative for CPVT in the next generation. Whole were treated with Nadolol 80\u202fmg per day, and the follow-up was uneventful after twenty-four months.\nThe Ryanodine Receptor type 2\u202fc.13823\u202fG>A, p.(Arg4608Gln) pathogenic variant is described in a malignant familial form of CRDS.",
    "authors": [
        {
            "affiliation": "Cardiology Department, Pasteur University Hospital, Nice, France. Electronic address: soksithikun@hotmail.com.",
            "firstname": "Sok-Sithikun",
            "initials": "SS",
            "lastname": "Bun"
        },
        {
            "affiliation": "Cardiology Department, Pasteur University Hospital, Nice, France.",
            "firstname": "Fabien",
            "initials": "F",
            "lastname": "Squara"
        },
        {
            "affiliation": "Cardiology Department, Pasteur University Hospital, Nice, France.",
            "firstname": "Didier",
            "initials": "D",
            "lastname": "Scarlatti"
        },
        {
            "affiliation": "Forensic Medicine Department, Archet University Hospital, Nice, France.",
            "firstname": "C\u00e9line",
            "initials": "C",
            "lastname": "Leccia"
        },
        {
            "affiliation": "Institut du Thorax, Centre Hospitalier Universitaire de Nantes, France.",
            "firstname": "Florence",
            "initials": "F",
            "lastname": "Kyndt"
        },
        {
            "affiliation": "Cardiology Department, Pasteur University Hospital, Nice, France.",
            "firstname": "Emile",
            "initials": "E",
            "lastname": "Ferrari"
        },
        {
            "affiliation": "Medical Genetic Department, Archet University Hospital, Universit\u00e9 C\u00f4te d'Azur, Nice, France; Inserm U1081, CNRS UMR7284, IRCAN, Universit\u00e9 C\u00f4te d'Azur, Nice, France.",
            "firstname": "C\u00e9cile",
            "initials": "C",
            "lastname": "Rouzier"
        }
    ],
    "conclusions": "The Ryanodine Receptor type 2\u202fc.13823\u202fG>A, p.(Arg4608Gln) pathogenic variant is described in a malignant familial form of CRDS.",
    "copyrights": "Copyright \u00a9 2025 The Authors. Published by Elsevier B.V. All rights reserved.",
    "doi": "10.1016/j.fsigen.2025.103238",
    "journal": "Forensic science international. Genetics",
    "keywords": [
        "Calcium release deficiency syndrome",
        "Cardiac arrest",
        "Catecholaminergic polymorphic ventricular tachycardia",
        "R4608 Mutation",
        "Ryanodine Receptor Type 2"
    ],
    "methods": null,
    "publication_date": "2025-02-17",
    "pubmed_id": "39956048",
    "results": null,
    "title": "Non-juvenile familial form of life-threatening arrhythmias caused by the Ryanodine Receptor type 2 c.13823 G>A, p.(Arg4608Gln) pathogenic variant: Atypical catecholaminergic polymorphic ventricular Tachycardia or misdiagnosis?",
    "xml": "<Element 'PubmedArticle' at 0x788503626e80>"
}