An autosomal recessive DNASE1L3-related autoimmune disease with unusual clinical presentation mimicking systemic lupus erythematosus.
We describe the third family in the world, after Arabian and Turkish ones, displaying an autosomal recessive autoimmune disease (AID), mimicking systemic lupus erythematosus (SLE), with unusual manifestations due to a homozygous frame-shift variant in DNASE1L3. SLE is a complex AID characterized by multiple organ involvement. Genetic risk variants identified account for only 15% of SLE heritability. Rare Mendelian forms have been reported, including DNASE1L3-related SLE. Through specific genetic tests we identified a homozygous 2 bp-deletion c.289_290delAC (NM_004944.2) in DNASE1L3, predicting frameshift and premature truncation (p.Thr97Ilefs*2). The same mutation was previously reported in three sisters, born from consanguineous parents and affected with hypocomplementemic urticarial vasculitis syndrome (HUVS). As approximately 50% of individuals affected with HUVS develop SLE, it is still unclear whether it is a SLE sub-phenotype or a separate condition.
1 Division of Rheumatology, Institute of Rheumatology, Catholic University School of Medicine, Rome, Italy.
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Carbonella
2 Division of Internal medicine, Institute of Medical Genetics, Catholic University School of Medicine, Rome, Italy.
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G
Mancano
1 Division of Rheumatology, Institute of Rheumatology, Catholic University School of Medicine, Rome, Italy.
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E
Gremese
3 Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
F S
FS
Alkuraya
3 Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
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Patel
2 Division of Internal medicine, Institute of Medical Genetics, Catholic University School of Medicine, Rome, Italy.
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F
Gurrieri
1 Division of Rheumatology, Institute of Rheumatology, Catholic University School of Medicine, Rome, Italy.
G
G
Ferraccioli
D000328:Adult; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000235:genetics; D004706:Endodeoxyribonucleases / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013577:Syndrome; D014581:Urticaria / Q000175:diagnosis / Q000235:genetics; D014657:Vasculitis / Q000175:diagnosis / Q000235:genetics
C485421:DNASE1L3 protein, human; D004706:Endodeoxyribonucleases
DNASE1L3; Systemic lupus erythematosus; hypocomplementemic urticarial vasculitis syndrome