Genetic Basis of Brain Malformations
Elena Parrini1, Valerio Conti1, William B Dobyns2
1Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Department of Neuroscience, A. Meyer Children's Hospital, University of Florence, Florence, Italy.
Molecular Syndromology
|October 27, 2016
Summary
Malformations of cortical development (MCD) cause significant disabilities. Genetic mutations affecting neuronal migration and organization are key factors in these complex brain disorders.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Malformations of cortical development (MCD) are a leading cause of developmental disabilities and epilepsy.
- These disorders stem from disruptions in crucial processes like cell proliferation, neuronal migration, and cortical organization.
Approach:
- Review of genetic associations with various MCD subtypes, including lissencephaly, heterotopia, and polymicrogyria.
- Focus on genes regulating microtubule and centrosome function (tubulinopathies) and the PI3K-AKT-mTOR pathway.
Key Points:
- Specific genes (e.g., LIS1, DCX, ARX, TUBA1A) are linked to diffuse neuronal migration disorders like lissencephaly.
- Tubulinopathies arise from mutations affecting microtubule synthesis and function.
- Other MCDs involve genes like ARFGEF2 and the PI3K-AKT-mTOR pathway, with postzygotic mutations playing a role.
Conclusions:
- MCDs are genetically diverse, impacting neuronal development and leading to varied neurological impairments.
- Identifying genetic causes is crucial for understanding and potentially treating these conditions.
Related Concept Videos
01:29Biological Causes of Schizophrenia
899
Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
899
01:30Neurulation
46.9K
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
46.9K
02:30Genomic Imprinting and Inheritance
38.4K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
38.4K
01:28Human Genetics
1.8K
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
1.8K
01:07Teratogenicity
4.4K
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
4.4K
01:11Genetic Lingo
116.6K
Overview
116.6K