A Novel Homozygous MYO7A Mutation: Case Report
MYO7A is an unconventional myosin that is essential for ordinary hearing and vision; mutations in the MYO7A gene result in Usher syndrome type 1B and other disorders. In this manuscript, we reported a mutation (c.4705delA) in exon 35, causing the alteration of a Ser amino acid to Ala at codon 1569 (p.H2027del) located within the first FERMdomain of the human protein myosin VIIA. This mutation involved in the pathogenesis of hearing loss, congenital night blindness, muscular weakness, skin problem, and difficulty in keeping balance in the 13-year-old female. After checkup the patient’s DNA was extracted from peripheral blood and amplification was performed by PCR. Sequencing method was performed for identification of the mutation. The c.4705delA mutation in exon 35 was found in the patient in heterozygosis form; this means that her mother and father were carriers. This mutation is located on the tail of the myosinVIIA protein and is associated with several disorders.
Well D, Blanchard S, Kaplan J, Guilford P, Gibson F, Walsh J, et al. Defective myosin VIIA gene responsible for Usher syndrome type IB. 1995.
Smith R, Berlin C, Hejtmancik J, Keats B, Kimberling WJ, Lewis R, et al. Clinical diagnosis of the Usher syndromes. American journal of medical genetics. 1994;50(1):32-8.
Street V, Kallman J, Kiemele K. Modifier controls severity of a novel dominant low-frequency MyosinVIIA (MYO7A) auditory mutation. Journal of medical genetics. 2004;41(5):e62-e.
Udovichenko IP, Gibbs D, Williams DS. Actin-based motor properties of native myosin VIIa. Journal of cell science. 2002;115(2):445-50.
Umeki N, Jung HS, Watanabe S, Sakai T, Li X-d, Ikebe R, et al. The tail binds to the head–neck domain, inhibiting ATPase activity of myosin VIIA. Proceedings of the National Academy of Sciences. 2009;106(21):8483-8.
Yang Y, Baboolal TG, Siththanandan V, Chen M, Walker ML, Knight PJ, et al. A FERM domain autoregulates Drosophila myosin 7a activity. Proceedings of the National Academy of Sciences. 2009;106(11):4189-94.
Sakai T, Umeki N, Ikebe R, Ikebe M. Cargo binding activates myosin VIIA motor function in cells. Proceedings of the National Academy of Sciences. 2011;108(17):7028-33.
Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H, et al. The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends in biochemical sciences. 1998;23(8):281-2.
Schwander M, Lopes V, Sczaniecka A, Gibbs D, Lillo C, Delano D, et al. A novel allele of myosin VIIa reveals a critical function for the C-terminal FERM domain for melanosome transport in retinal pigment epithelial cells. The Journal of Neuroscience. 2009;29(50):15810-8.
El-Amraoui A, Sahly I, Picaud S, Sahel J, Abitbol M, Petit C. Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells. Human molecular genetics. 1996;5(8):1171-8.
Hasson T. Unconventional myosins, the basis for deafness in mouse and man. American journal of human genetics. 1997;61(4):801.