Molecular genetic decoding of malformations of cortical development

Abstract

Molecular genetic decoding of malformations of cortical development Malformations of cortical development (MCD) cover a broad spectrum of developmental disorders which cause the various clinical manifestations including epilepsy, developmental delay, and intellectual disability. MCD have been clinically classiἀed based on the disruption of developmental processes such as proliferation, migration, and organization. Molecular genetic studies of MCD have improved our understanding of these disorders at a molecular level beyond the clinical classiἀcation. These recent advances are resulted from the development of massive parallel sequencing technology, also known as next-generation sequencing (NGS), which has allowed researchers to uncover novel molecular genetic pathways associated with inherited or de novo mutations. Although an increasing number of disease-related genes or genetic variations have been identiἀed, genotype-phenotype correlation is hampered when the biological or pathological functions of identiἀed genetic variations are not fully understood. To elucidate the causality of genetic variations, in vivo disease models that reḀect these variations are required. In the current review, we review the use of NGS technology to identify genes involved in MCD, and discuss how the functions of these identiἀed genes can be validated through in vivo disease modeling.