De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene

• Published in: Brain (London, England : 1878) Vol. 141; no. 7; pp. 1998 - 2013
• Main Authors: Chemin, Jean, Siquier-Pernet, Karine, Nicouleau, Michaël, Barcia, Giulia, Ahmad, Ali, Medina-Cano, Daniel, Hanein, Sylvain, Altin, Nami, Hubert, Laurence, Bole-Feysot, Christine, Fourage, Cécile, Nitschké, Patrick, Thevenon, Julien, Rio, Marlène, Blanc, Pierre, vidal, Céline, Bahi-Buisson, Nadia, Desguerre, Isabelle, Munnich, Arnold, Lyonnet, Stanislas, Boddaert, Nathalie, Fassi, Emily, Shinawi, Marwan, Zimmerman, Holly, Amiel, Jeanne, Faivre, Laurence, Colleaux, Laurence, Lory, Philippe, Cantagrel, Vincent
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.07.2018
• Subjects: Adolescent; Adult; Atrophy - pathology; Brain - pathology; Calcium - metabolism; Calcium Channels - genetics; Calcium Channels, T-Type - genetics; Calcium Channels, T-Type - metabolism; Cerebellar Ataxia - genetics; Cerebellar Ataxia - physiopathology; Cerebellar Diseases - complications; Cerebellum - pathology; Child; Child, Preschool; Cohort Studies; Developmental Disabilities - genetics; Female; Gain of Function Mutation - genetics; Genetics; Humans; Intellectual Disability - genetics; Life Sciences; Male; Microcephaly - genetics; Mutation; Pedigree; Phenotype; Purkinje Cells - pathology; voltage-gated calcium channel; mutation; cerebellar atrophy; 3.1; Ca; de novo mutation; Cav3.1; CACNA1G

Using gene panel and whole exome sequencing, Chemin et al. show that de novo events are a major genetic cause of childhood-onset cerebellar atrophy. De novo gain of function mutations in the calcium channel CACNA1G/Cav3.1 give rise to a cerebellar syndrome via a potentially druggable disease mechani...