کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2821328 | 1160941 | 2009 | 5 صفحه PDF | دانلود رایگان |
Hemophilia B has been considered as a classical monogenic disorder with complete penetrance. Here, we observed that its allelic spectrum encompasses mutations that show least phenotypic variation as well as those showing phenotypic plasticity, thereby establishing hemophilia B as a quasi-quantitative condition with variable expressivity. Thus, we relocate it from simple monogenic diseases with complete penetrance into a space that marks the conceptual continuum of Mendelian to complex diseases. By computational analysis, we show that mutations showing phenotypic variation were characterized by relatively less conserved mutant sites and more tolerated conservative substitutions. We also demonstrate that consideration of continuous phenotypes renders quantitative rigor for interrogation and hence higher predictive value while analyzing for differential properties than classifications based on clinical end points. Certain mutations have been consistently reported to cause mild phenotype, calling for a check in indiscriminate termination of fetuses following prenatal diagnosis.
Journal: Genomics - Volume 94, Issue 6, December 2009, Pages 433–437