OBJECTIVE: Hypocomplementemic urticarial vasculitis syndrome (HUVS) is characterized by recurrent urticaria along with dermal vasculitis, arthritis, and glomerulonephritis. Systemic lupus erythematosus (SLE) develops in >50% of patients with HUVS, although the pathogenesis is unknown. The aim of this study was to identify the causative DNA mutations in 2 families with autosomal-recessive HUVS, in order to reveal the pathogenesis and facilitate the laboratory diagnosis. METHODS: Autozygosity mapping was combined with whole-exome sequencing. RESULTS: In a family with 3 affected children, we identified a homozygous frameshift mutation, c.289_290delAC, in DNASE1L3. We subsequently identified another homozygous DNASE1L3 mutation leading to exon skipping, c.320+4delAGTA, in an unrelated family. The detected mutations led to loss of function, via either nonsense-mediated messenger RNA decay or abolished endonuclease activity, as demonstrated by a plasmid nicking assay. CONCLUSION: These results show that HUVS is caused by mutations in DNASE1L3, encoding an endonuclease that previously has been associated with SLE.
OBJECTIVE:Hypocomplementemic urticarial vasculitis syndrome (HUVS) is characterized by recurrent urticaria along with dermal vasculitis, arthritis, and glomerulonephritis. Systemic lupus erythematosus (SLE) develops in >50% of patients with HUVS, although the pathogenesis is unknown. The aim of this study was to identify the causative DNA mutations in 2 families with autosomal-recessive HUVS, in order to reveal the pathogenesis and facilitate the laboratory diagnosis. METHODS: Autozygosity mapping was combined with whole-exome sequencing. RESULTS: In a family with 3 affected children, we identified a homozygous frameshift mutation, c.289_290delAC, in DNASE1L3. We subsequently identified another homozygous DNASE1L3 mutation leading to exon skipping, c.320+4delAGTA, in an unrelated family. The detected mutations led to loss of function, via either nonsense-mediated messenger RNA decay or abolished endonuclease activity, as demonstrated by a plasmid nicking assay. CONCLUSION: These results show that HUVS is caused by mutations in DNASE1L3, encoding an endonuclease that previously has been associated with SLE.
Authors: John T Crowl; Elizabeth E Gray; Kathleen Pestal; Hannah E Volkman; Daniel B Stetson Journal: Annu Rev Immunol Date: 2017-01-30 Impact factor: 28.527
Authors: Chetna Soni; Oriana A Perez; William N Voss; Joseph N Pucella; Lee Serpas; Justin Mehl; Krystal L Ching; Jule Goike; George Georgiou; Gregory C Ippolito; Vanja Sisirak; Boris Reizis Journal: Immunity Date: 2020-05-25 Impact factor: 31.745
Authors: Vanja Sisirak; Benjamin Sally; Vivette D'Agati; Wilnelly Martinez-Ortiz; Z Birsin Özçakar; Joseph David; Ali Rashidfarrokhi; Ada Yeste; Casandra Panea; Asiya Seema Chida; Milena Bogunovic; Ivaylo I Ivanov; Francisco J Quintana; Inaki Sanz; Keith B Elkon; Mustafa Tekin; Fatoş Yalçınkaya; Timothy J Cardozo; Robert M Clancy; Jill P Buyon; Boris Reizis Journal: Cell Date: 2016-06-09 Impact factor: 41.582