Unusual clinical description of adult with Timothy syndrome, carrier of a new heterozygote mutation of CACNA1C.

Cindy Colson, Hervé Mittre, Adeline Busson, Antoine Leenhardt, Isabelle Denjoy, Véronique Fressard, Yann Troadec

Journal: European journal of medical genetics 2019;62(7):103648

PMID: 30998997

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Abstract

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.

Address: Service Génétique, Génétique Clinique, CHU, Caen, France; Normandy University, UNICAEN, BIOTARGEN, Caen, France. Electronic address: [email protected].; Service Génétique, Génétique Moléculaire, CHU, Caen, France.; Service de Génétique Clinique, Hôpital Erasme, Bruxelles, Belgium.; Service de cardiologie, Hôpital Xavier Bichat-Claude Bernard, Paris, France.; Centre de génétique moléculaire et chromosomique, UF cardiogénétique et myogénétique moléculaire et cellulaire, Hôpital Pitié-Salpétrière, Paris, France.; Service Génétique, Génétique Clinique, CHU, Caen, France; Normandy University, UNICAEN, BIOTARGEN, Caen, France.

DOI: 10.1016/j.ejmg.2019.04.005

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MeSH Terms: Adult, Autistic Disorder, Calcium Channels, L-Type, Female, Heterozygote, Humans, Long QT Syndrome, Mutation, Phenotype, Plakophilins, Syndactyly