Which genetic mutation is primarily associated with Progeria?

Progeria, specifically Hutchinson-Gilford Progeria Syndrome (HGPS), is primarily associated with mutations in the LMNA gene. This gene encodes for lamin A, a protein that is crucial for maintaining the structural integrity of the nuclear envelope. The specific mutation linked to Progeria is a single nucleotide mutation that results in the production of an abnormal form of lamin A known as progerin. This abnormal protein leads to severe developmental and physical changes that mimic aspects of aging at an accelerated rate.

The association of LMNA with Progeria highlights the significance of nuclear stability and elasticity in normal cellular function and development. Therefore, individuals with Progeria exhibit symptoms that relate to both premature aging and cellular dysfunction, which are primarily driven by the defective lamin A protein that arises from mutations in this gene.

In contrast, mutations in MECP2 are primarily associated with Rett syndrome, mutations in GNAS are linked to various disorders including Albright hereditary osteodystrophy, and mutations in RBM8A are connected to a different set of genetic disorders. These genes do not play a role in the pathology of Progeria, further underscoring the specificity of LMNA mutations to this condition.