Clinical heterogeneity among a three-generation Japanese family with D18N TREX1 mutation for Aicardi-Goutières syndrome / familial chilblain lupus
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چکیده
Background Aicardi-Goutières syndrome (AGS) is a genetic disease, characterized by encephalopathy with cerebral calcification, white matter abnormalities, cerebral atrophy, elevated interferon-alpha in the cerebrospinal fluid and chilblain. Most of AGS patients have severe neurological findings including developmental delay. Five genes, namely TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SAMHD1 have been reported to be responsible for AGS. Most cases of AGS are inherited as autosomal recessive manner, although autosomal dominant AGS is rarely reported and its clinical manifestations are largely unknown.
منابع مشابه
Aicardi–Goutières syndrome protein TREX1 suppresses L1 and maintains genome integrity through exonuclease-independent ORF1p depletion
Maintaining genome integrity is important for cells and damaged DNA triggers autoimmunity. Previous studies have reported that Three-prime repair exonuclease 1(TREX1), an endogenous DNA exonuclease, prevents immune activation by depleting damaged DNA, thus preventing the development of certain autoimmune diseases. Consistently, mutations in TREX1 are linked with autoimmune diseases such as syst...
متن کاملThe TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease.
Mutations in TREX1 have been linked to a spectrum of human autoimmune diseases including Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus, and retinal vasculopathy and cerebral leukodystrophy. A common feature in these conditions is the frequent detection of antibodies to double-stranded DNA (dsDNA). TREX1 participates in a cell death process implic...
متن کاملNew roles for the major human 3'-5' exonuclease TREX1 in human disease.
Aicardi-Goutières syndrome (AGS), Systemic Lupus Erythematosus (SLE), Familial Chilblain Lupus (FCL) and Retinal Vasculopathy and Cerebral Leukodystrophy (RVCL) {a new term encompassing three independently described conditions with a common etiology--Cerebroretinal Vasculopathy (CRV), Hereditary Vascular Retinopathy (HVR) and Hereditary Endotheliopathy, Retinopathy and Nephropathy (HERNS)}--hav...
متن کاملPhenotypic variation in familial chilblain lupus (FCL) and Aicardi-Goutières syndrome (AGS) associated with TREX1 mutation in 4 family members
Results The index case was a 10 year old Afro-Caribbean boy who initially presented with a non-progressive developmental delay and severe chilblains (the chilblains improved with methotrexate). He developed transient acute ataxia and flattened affect, with visual and auditory hallucinations. Parotid swelling, arthritis and proximal myopathy were noted, but autoantibodies were negative and compl...
متن کاملRAPID COMMUNICATIONS A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus
We recently described a novel autosomal-dominant genodermatosis, termed familial chilblain lupus, and mapped its genetic locus to chromosome 3p21. Familial chilblain lupus manifests in early childhood with ulcerating acral skin lesions and is associated with arthralgias and circulating antinuclear antibodies. In this study, we report the identification of a heterozygous missense mutation (D18N)...
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