Micaglio Emanuele, Monasky Michelle M, Ciconte Giuseppe, Vicedomini Gabriele, Conti Manuel, Mecarocci Valerio, Giannelli Luigi, Giordano Federica, Pollina Alberto, Saviano Massimo, Crisà Simonetta, Borrelli Valeria, Ghiroldi Andrea, D'Imperio Sara, Di Resta Chiara, Benedetti Sara, Ferrari Maurizio, Santinelli Vincenzo, Anastasia Luigi, Pappone Carlo
Arrhythmology Department, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
Stem Cells for Tissue Engineering Laboratory, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
Front Genet. 2019 Feb 15;10:50. doi: 10.3389/fgene.2019.00050. eCollection 2019.
In this case series, we report for the first time a family in which the inherited nonsense mutation [c. 3946C > T (p.Arg1316*)] in the gene segregates in association with Brugada syndrome (BrS). Moreover, we also report, for the first time, the frameshift mutation [c.7686delG (p.Ile2563fsX40)] in the gene, as well as its association with type 1 neurofibromatosis (NF1), characterized by pigmentary lesions (café au lait spots, Lisch nodules, freckling) and cutaneous neurofibromas. Both of these mutations and associated phenotypes were discovered in the same family. This genetic association may identify a subset of patients at higher risk of sudden cardiac death who require the appropriate electrophysiological evaluation. This case series highlights the importance of genetic testing not only to molecularly confirm the pathology but also to identify asymptomatic family members who need clinical examinations and preventive interventions, as well as to advise about the possibility of avoiding recurrence risk with medically assisted reproduction.
在这个病例系列中，我们首次报告了一个家族，该家族中基因的遗传性无义突变[c. 3946C>T (p.Arg1316*)]与Brugada综合征（BrS）相关联。此外，我们还首次报告了该基因中的移码突变[c.7686delG (p.Ile2563fsX40)]，以及它与1型神经纤维瘤病（NF1）的关联，1型神经纤维瘤病的特征是色素沉着病变（牛奶咖啡斑、Lisch结节、雀斑）和皮肤神经纤维瘤。这两种突变及相关表型均在同一个家族中被发现。这种基因关联可能会识别出一部分有更高心脏性猝死风险的患者，他们需要进行适当的电生理评估。这个病例系列强调了基因检测的重要性，不仅在于从分子层面确认病理情况，还在于识别需要临床检查和预防性干预的无症状家庭成员，以及就通过医学辅助生殖避免复发风险的可能性提供建议。
