Reflections: Tetra-Amelia

Last week in our Developmental Biology class, we did presentations on different topics. I did my presentation on Tetra-Amelia. Tetra-Amelia is an autosomal recessive disorder that has the phenotypic results of absence of all four limbs. Tetra-Amelia causes severe malformations in the face, head, heart, nervous system,skeleton, genitalia and lungs. It is caused by a mutatio on the WNT3 gene.
In class we studied the WNT pathway. The WNT genes play a critical role in development before birth. It gives instructions to make proteins that will be a part of the WNT chemical signaling pathway. The WNT3 gene is specific to creating certain genes that are responsible for the development of limbs.

The WNT proteins are ligands and are able to bidn to receptors on other proteins. They bind to the receptor frizzled protein. This binding to frizzled causes the activation of the disheveled protein. Disheveled then inhibits glycogen synthase kinase 3 (GSK3). When GSK3 is inactive, B-catenin is free to associate with an LEF or TCF protein. This association with the two proteins acts like and becomes a transcription factor. These cascade of effects causes growth and division of cells that will later determine what those cells will differentiate into. The WNT3 gene is critical for outgrowth of limbs and is critical for determining the anterior-posterior axis. IT has five exons and encodes for a protein that has 355 amino acids. When the sequence of WNT3 was done, a nonsense mutation was found. The nonsense mutation at codon 83 created a premature stop codon. This causes only 82 amino acids to be produced instead of 355 amino acids