Fibroblast büyüme faktörü 3 (FGF3) geninde tanımlanan L6P ve S156P mutasyonlarının etkilerinin ın vıtro analizi
Özet
Hearing loss and deafness are global issues that affect at least 278 million people worlwide. Two third of these people live in developed countries (Tucci vd 2010). Screening of newborns for hearing loss in these countries have shown that congenital hearing loss affects 1,33-1,86 of 1000 children. Hearing loss can occur congenitally or postnatally. Genetic causes account for approximately %50-60 of congenital hearing loss. Approximately 30% of the genetically caused hearing loss is accompanied by other clinical findings and these cases are referred to as syndromic hearing loss (Nance 2003).A new autosomal recessive syndrome with type I microtia (shortening of auricles), microdontia, and profound congenital deafness associated with a complete labyrinth aplasia have been discovered in 2007 (OMIM 610706, LAMM (Deafness with Labyrinthine Aplasia, Microtia, and Microdontia, (Tekin vd 2007)) and it has also been shown that homozygous mutations causing this autosomal recessive syndrome are in the fibroblast growth factor 3 (FGF3) gene (Tekin vd 2008). FGF3 protein, which is encoded by FGF3 gene, is a secreted protein that is expressed at the embryonic stage. In this study, the in vitro effects of two previously identified missense mutations, p.L6P and p.S156P, on secretion of this protein were investigated. After these two mutations were mimiced by site-directed mutagenesis, mutant proteins have subsequently been expressed in cell culture, normal and mutant FGF3 proteins are analyzed for determining the intracellular localization and the quantification. As a result, in contrast to the normal protein, it was found that there have been differences for localization and quantification in mutant FGF3 proteins.