Item request has been placed!
×
Item request cannot be made.
×
Processing Request
CACNA1A haploinsufficiency causes cognitive impairment, autism and epileptic encephalopathy with mild cerebellar symptoms.
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
- Author(s): Damaj, Lena; Lupien-Meilleur, Alexis; Lortie, Anne; Riou, Émilie; Ospina, Luis H; Gagnon, Louise; Vanasse, Catherine; Rossignol, Elsa
- Source:
European Journal of Human Genetics. Nov2015, Vol. 23 Issue 11, p1505-1512. 8p.
- Additional Information
- Subject Terms:
- Abstract:
CACNA1A loss-of-function mutations classically present as episodic ataxia type 2 (EA2), with brief episodes of ataxia and nystagmus, or with progressive spinocerebellar ataxia (SCA6). A minority of patients carrying CACNA1A mutations develops epilepsy. Non-motor symptoms associated with these mutations are often overlooked. In this study, we report 16 affected individuals from four unrelated families presenting with a spectrum of cognitive impairment including intellectual deficiency, executive dysfunction, ADHD and/or autism, as well as childhood-onset epileptic encephalopathy with refractory absence epilepsy, febrile seizures, downbeat nystagmus and episodic ataxia. Sequencing revealed one CACNA1A gene deletion, two deleterious CACNA1A point mutations including one known stop-gain and one new frameshift variant and a new splice-site variant. This report illustrates the phenotypic heterogeneity of CACNA1A loss-of-function mutations and stresses the cognitive and epileptic manifestations caused by the loss of CaV2.1 channels function, presumably affecting cerebellar, cortical and limbic networks. [ABSTRACT FROM AUTHOR]
No Comments.