This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
FRMD7 Gene
The FRMD7 gene contains a FERM domain, which is named for the four original proteins in which it was originally described. This FERM domain contains three subdomains that interact to form a single molecule. This domain is usually related with proteins associated with the cytoskeleton. In particular, the FERM domain links to actin filaments and adhesion proteins in the cytoskeleton [1].
FRMD7 itself has 12 exons which encode a 714 polypeptide chain [Accession Number: NP_919253]. The specific function of FRMD7 is not well understood but several studies suggest it plays an important role in neuronal development, particularly in regions associated with ocular movement. The most common mutations in FRMD7 are point missense mutations that cause an amino acid change at that location. Figure 2 also shows a mutation where exon 2 is skipped due to an introduced splice site on the primary mRNA transcript with a point mutation [2].
In both the human and mouse embryonic brains, FRMD7 is specially and temporally regulated, and in culture the protein is strongly associated with the growth cone of developing neurons [3]. What this means is, a mutation in the FRMD7 protein can lead to stunted axon growth and immature neuron cells. This can lead directly to infantile nystagmus since FRMD7 is associated with ocular movement.
References
[1] Hamada, K., Shimizu, T., Matsui, T., Tsukita, S., Tsukita, S., Hakoshima, T. (2000)
Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain. European Molecular Biology Organization Journal, 19(2000), 4449. doi: 10.1093/emboj/19.17.4449
[2] Thomas, M. G., Crosier, M., Lindsay, S., Kumar, A., Thomas, S., Araki, M., Talbot, C., McLean, R. J., Surendran, M., Taylor, K., Leroy, B. P., Moore, A. T., Hunter, D. G., Hertle, R. W., Tarpey, P., Langmann, A., Lindner, S., Brandner, M., Gottlob., I. (2011)
The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus. Brain, a Journal of Neurology, 2011(134), 892, doi: 10.1093/brain/awq373
[3] Betts-Henderson J., Bartesaghi, S., Crosier, M., Lindsay, S., Chen, H., Salomoni, P., Gottlob, I., Nicotera P. (2010)
The nystagmus-associated FRMD7 gene regulates neuronal outgrowth and development. Human Molecular Genetics, 19(2), 342. doi: 10.1093/hmg/ddp500
Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain. European Molecular Biology Organization Journal, 19(2000), 4449. doi: 10.1093/emboj/19.17.4449
[2] Thomas, M. G., Crosier, M., Lindsay, S., Kumar, A., Thomas, S., Araki, M., Talbot, C., McLean, R. J., Surendran, M., Taylor, K., Leroy, B. P., Moore, A. T., Hunter, D. G., Hertle, R. W., Tarpey, P., Langmann, A., Lindner, S., Brandner, M., Gottlob., I. (2011)
The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus. Brain, a Journal of Neurology, 2011(134), 892, doi: 10.1093/brain/awq373
[3] Betts-Henderson J., Bartesaghi, S., Crosier, M., Lindsay, S., Chen, H., Salomoni, P., Gottlob, I., Nicotera P. (2010)
The nystagmus-associated FRMD7 gene regulates neuronal outgrowth and development. Human Molecular Genetics, 19(2), 342. doi: 10.1093/hmg/ddp500
Site created by: Kristen Klimo
Last updated: 5/11/2011
University of Wisconsin-Madison
Last updated: 5/11/2011
University of Wisconsin-Madison