Platelet-derived Growth Factor Receptor Alpha Gene Mutations in Vitiligo Vulgaris

Abstract

Vitiligo vulgaris is an acquired depigmenting disorder resulting from the loss of melanocytes in the skin. Though several putative susceptibility loci of vitiligo have been identified in different populations, the pathogenesis of the disease remains poorly understood. Through genetic linkage analysis of a large Chinese family cohort of vitiligo, we identified a vitiligo linkage locus AIS4 within chromosome 4q12-q21, a region containing several possible candidate genes, including the platelet-derived growth factor receptor alpha (PDGFRA) gene. We postulated that PDGFR mutations may be linked with vitiligo. To test this hypothesis, we performed DNA sequencing on this gene in 143 multiplex families with familial vitiligo vulgaris, 480 patients with sporadic vitiligo vulgaris, and 480 healthy subjects. Mutations were found in 3.5% of familial vitiligo cases, which is significantly higher than for the general population (0.42%, p = 0.008, Fisher's exact test), and possibly higher than in sporadic vitiligo patients (1.0%, p = 0.053). To our knowledge, this is the first observation that PDGFRA mutations are linked with familial vitiligo vulgaris.

Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

“…There is evidence that vitiligo is an autoimmune disease [6], [7], [8], [9], [10], [11], [12], [13], [14], possibly involving additional factors such as oxidative stress [15] and genetic predisposition [6], [10], [11], [12], [13], [16], [17], [18]. The autoimmune hypothesis stems from the frequently observed association with other autoimmune diseases, such as hypothyroidism and diabetes [19], [20], [21], [22], [23].…”

Genetics of Vitiligo

“…These investigators suggested that AIS4 might be PDGFRA [58], though this seems much less likely than KIT . The chromosome 6 locus may correspond to the MHC.…”

Modern vitiligo genetics sheds new light on an ancient disease

“…studied XBP1 as a candidate gene within the 22q12 linkage region, though this assignment has not yet been confirmed. Xu et al . studied PDGFRA as a candidate gene within the 4q12‐q21 linkage region, finding more variation in familial vitiligo cases than controls.…”