Expanding the spectrum of Grik2 mutations: intellectual disability, behavioural disorder, epilepsy and dystonia.

CÓRDOBA MARTA; RODRIGUEZ QUIROGA SERGIO

CLINICAL GENETICS

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2015

0009-9163

Intellectual disability (ID) is a common neurodevelopmental disorder that involves impairments of general mental abilities that impact adaptive functioning. Noteworthy advances in the research of the genetic causes of non-syndromic ID have been observed in recent years. Most of these advances have depended on the introduction of next generation sequencing technologies, which have revolutionized this field allowing the identification of causative DNA mutations in several new genes. Some of them are related to glutamatergic neurotransmission, such as GRIK2, which was proposed as the genetic cause of isolated moderate to severe ID in an Iranian family. However, it still remains unclear, which are, if any, the typical phenotypic features linked to defects on glutamate pathways. The spectrum seems to be very wide including epilepsy, ID and psychiatric disorders. Furthermore, occasional clinical-genetic descriptions in unique families need to be confirmed and expanded in other non-related subjects before the genetic cause of a familial disorder could be confidently established. We report here clinical features present in two siblings from a consanguineous family affected with variable degrees of cognitive impairment, epilepsy, dystonia and behavioral disorders where a homozygous non-sense mutation in the ionotropic glutamate receptor type 6 gene, GRIK2, was identified through whole-exome sequencing