Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome.

Abstract

TREX1 constitutes the major 3'-->5' DNA exonuclease activity measured in mammalian cells. Recently, biallelic mutations in TREX1 have been shown to cause Aicardi-Goutieres syndrome at the AGS1 locus. Interestingly, Aicardi-Goutieres syndrome shows overlap with systemic lupus erythematosus at both clinical and pathological levels. Here, we report a heterozygous TREX1 mutation causing familial chilblain lupus. Additionally, we describe a de novo heterozygous mutation, affecting a critical catalytic residue in TREX1, that results in typical Aicardi-Goutieres syndrome.

• Authors: Gillian Rice, William G Newman, John Dean, Teresa Patrick, Rekha Parmar, Kim Flintoff, Peter Robins, Scott Harvey, Thomas Hollis, Ann O'Hara, Ariane L Herrick, Andrew P Bowden, Fred W Perrino, Tomas Lindahl, Deborah E Barnes, Yanick J Crow
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 80 Issue 4 Pg. 811-5 (Apr 2007) ISSN: 0002-9297 [Print] United States
• PMID: 17357087 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphoproteins
• Exodeoxyribonucleases
• three prime repair exonuclease 1

Topics

• Basal Ganglia Diseases (complications, genetics, pathology)
• Base Sequence
• Cell Line
• Exodeoxyribonucleases (genetics)
• Female
• Genetic Predisposition to Disease
• Humans
• Lupus Erythematosus, Systemic (complications, genetics, pathology)
• Male
• Molecular Sequence Data
• Mutation (genetics)
• Pedigree
• Phosphoproteins (genetics)
• Sequence Analysis, DNA
• Syndrome