Resumen

Fibroblast growth factor receptor (FGFR) gain-of-function mutations form the pathogenic basis of multiple congenital pathologies. A pioneering body of work over the past two decades has established that a unique mutation selection process within the testis likely underlies the paternal age effect characteristics of such diseases. This mechanism, analogous to positive selection of mutations promoting proliferation in tumorigenesis, sparked interest in mutation profiling of testicular and other cancers. The resulting discovery of FGFR gain-of-function mutations akin to those of congenital syndromes has enabled a novel hypothesis to be born: that mutations represent a spectrum of activation. As such, FGFR gain-of-function mutations could be pathogenic not solely in defined monogenic syndromes but within myriad disease processes with ‘low activation’ conferring increased disease risk. Do such mutations contribute to multigenic risk in multiple pathologies? This review evaluates this hypothesis, alluding to the plausible clinical implications that ensue.

Palabras clave: Fibroblast growth factors Acrocephalosyndactylia craniosynostoses Germ-Line Mutation.

2013-11-11   |   1,621 visitas   |   Evalua este artículo 0 valoraciones

Vol. 1 Núm.3. Diciembre 2013 Pags. 123-127 Int J Med Students 2013; 1(3)