Colson Cindy, Mittre Hervé, Busson Adeline, Leenhardt Antoine, Denjoy Isabelle, Fressard Véronique, Troadec Yann
Service Génétique, Génétique Clinique, CHU, Caen, France; Normandy University, UNICAEN, BIOTARGEN, Caen, France.
Service Génétique, Génétique Moléculaire, CHU, Caen, France.
Eur J Med Genet. 2019 Jul;62(7):103648. doi: 10.1016/j.ejmg.2019.04.005. Epub 2019 Apr 16.
CANAC1C encodes for the main cardiac L-type calcium channel and mutations on it lead to a prolonged QT interval in Timothy Syndrome (TS). We provide a new de novo constitutional heterozygote missense variation in CACNA1C in a living adult woman, also carrier of the known c.2146-1G>C heterozygous variation of PKP2 inherited from her father. To our knowledge, this patient is the first to have the two variations in these genes. Theses clinical and molecular findings expand the clinical and molecular spectrum of TS and show the interest of next generation sequencing or whole exome sequencing in rare disorders, atypical or novel phenotype.
CANAC1C编码主要的心脏L型钙通道，其上的突变会导致 Timothy 综合征（TS）患者出现QT间期延长。我们在一名成年女性活体中发现了一种新的CACNA1C基因新生性体质杂合错义变异，她也是从父亲那里遗传了已知的PKP2基因c.2146-1G>C杂合变异的携带者。据我们所知，该患者是首例在这些基因中同时存在这两种变异的病例。这些临床和分子学发现扩展了TS的临床和分子谱，并显示了下一代测序或全外显子测序在罕见疾病、非典型或新表型研究中的价值。
