A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome

Progeria is a fatal premature aging disease caused by mutations in the LMNA gene, leading to production of the toxic protein progerin.    We describe a child with a mixed cell population (mosaicism) carrying two different progerin-producing mutations of the same nucleotide – one causing clinically severe Progeria and one milder Progeria.  The child possessed intermediate disease characteristics.  We postulate that the severe mutation represents the original genotype, and the milder variant arose early in embryogenesis and was subjected to positive selection.  This type of mosaicism has not been previously characterized for any disease. Such compensatory mechanisms may occur elsewhere, but go undetected by current genetic screens. (By Dr. Leslie B. Gordon, http://jmg.bmj.com/content/early/2016/12/05/jmedgenet-2016-104295 )