Inborn errors of development: disruption of pathways critical for normal development
1Department of Pediatrics, Center for Human Genetics and Genomics, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0627, USA. awynshawboris@ucsd.edu
Pediatric Clinics of North America
|October 10, 2006
Summary
Congenital birth defects arise from disruptions in evolutionarily conserved developmental pathways. Understanding these signal transduction pathways helps link genetic functions to developmental disorders in children.
Area of Science:
- Developmental Biology
- Genetics
- Pediatrics
Background:
- Congenital birth defects were historically classified descriptively.
- Genetic and environmental factors influencing birth defects are increasingly understood.
- Many causative genes are involved in conserved developmental signal transduction pathways.
Purpose of the Study:
- To provide a framework for understanding birth defects.
- To link observed phenotypes in developmental disorders to gene function.
- To focus on three key conserved signal transduction pathways.
Main Methods:
- Review of genetic and molecular data on birth defects.
- Analysis of conserved signal transduction pathways.
- Integration of pathway function with developmental phenotypes.
Main Results:
- Identified conserved signal transduction pathways crucial for development.
- Demonstrated that malformations can be viewed as inborn errors of development.
- Established relationships between specific pathways and observed phenotypes.
Conclusions:
- Conserved signal transduction pathways are fundamental to normal development.
- Disruptions in these pathways lead to congenital birth defects.
- This pathway-centric approach aids in understanding developmental disorders.
Related Concept Videos
01:20Inborn Errors of Metabolism
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
01:07Teratogenicity
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...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
02:30Genomic Imprinting and Inheritance
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...
01:30Neurulation
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 anterior...
02:46Genome Copying Errors
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.