Scott Harvey

TL;DR: This work reports monoallelic frameshift or missense mutations and one 3′ UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls, and demonstrates that two mutant TREx1 alleles alter subcellular targeting.

TL;DR: A de novo heterozygous mutation, affecting a critical catalytic residue in TREX1, that results in typical Aicardi-Goutieres syndrome is described.

TL;DR: Lymphoblastoid cells carrying the D18N mutation are significantly less sensitive to granzyme A-mediated cell death, suggesting a novel role for this caspase-independent form of apoptosis in the pathogenesis of familial chilblain lupus.

TL;DR: The D200N- and D18N-containing TREX1 homo- and heterodimers inhibit the dsDNA degradation activity of TREX2WT enzyme, providing a likely explanation for the dominant phenotype of these TREx1 mutant alleles in AGS and FCL.

TL;DR: The x-ray crystal structure of the dimeric mouse TREX1 protein in substrate and product complexes containing single-stranded DNA and deoxyadenosine monophosphate shows specific interactions between the bound nucleotides and the residues lining the binding pocket of the 3′ terminal nucleotide within the enzyme active site that account for specificity, and provide the molecular basis for understanding mutations that lead to disease.