Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B).
A novel missense mutation in LIS1 in a child with subcortical band heterotopia and pachygyria inherited from his mildly affected mother with somatic mosaicism.
Mutation analysis of LIS1, using highly sensitive techniques such as denaturing high-pressure liquid chromatography, should be considered for patients with posteriorly predominant subcortical band heterotopia and pachygyria.
Our findings identify CTNNA2 as the first catenin family member with biallelic mutations in humans, causing a new pachygyria syndrome linked to actin regulation, and uncover a key factor involved in ARP2/3 repression in neurons.
Our findings identify CTNNA2 as the first catenin family member with biallelic mutations in humans, causing a new pachygyria syndrome linked to actin regulation, and uncover a key factor involved in ARP2/3 repression in neurons.
Whilst many of these pathogenic DCX mutations are within the doublecortin domains (DC1 and DC2) that mediate direct DCX-MT association, a pathogenic mutation DCX E2K that causes cognitive impairment and pachygyria in human patients lies within the regulatory DCX N-terminus (DCX-N) preceding the DC1 domain.
Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B).
The most prominent radiological phenotype was an anteriorly predominant pachygyria or agyria (54.5%) although DCX-associated lissencephaly encompasses a complete range of LIS grades.
Mutations of TUBA1A gene were first identified as causing a distinctive neuroradiologic phenotype characterized by cortical abnormalities ranging from classical lissencephaly to perisylvian pachygyria with dysgenetic corpus callosum, brainstem and cerebellum.
De novo mutations in the TUBA1A gene are responsible for a wide spectrum of neuronal migration disorders, ranging from lissencephaly to perisylvian pachygyria.