关键词: DNASE1L3基因, 狼疮性肾炎, 致病变异, 肺出血

Abstract: Ｏｂｊｅｃｔｉｖｅ：To analyze clinical and genetic features of a patient with lupus nephritis due to DNASE1L3 mutation.
Ｍｅｔｈｏｄｏｌｏｇｙ：Whole exome sequencing was carried out to detect genetic variants of a patient with lupus nephritis and pulmonary haemorrhage. The clinical characteristics and pathogenic variants spectrum of patients with lupus nephritis due to DNASE1L3 deficiency were summarized.
Ｒｅｓｕｌｔｓ：A male patient with lupus nephritis, onset at the age of 23. He presented with massive proteinuria and microscopic hematuria. Kidney biopsy showed lupus nephritis type V+IV. Other manifestations include pulmonary haemorrhage, severe anemia, urticarialike rash and arthritis. Whole exome sequencing detected a novel pathogenic homozygous variant c.565_568del (p.D189Sfs*17) in DNASE1L3 gene. The literature review of 25 reported cases of DNASE1L3 deficiency causing lupus nephritis, combined with present case, a total of 9 pathogenic variants in DNASE1L3 gene were identified. 53.8% were male, 786％ had hematologic involvement, 71.4％ had joint involvement, 71.4％ had urticaria, 42.9％ had pulmonary involvement, 357％ had gastrointestinal involvement, 21.4％ had ocular involvement, 21.4％ had cardiac involvement, and 57.7％ had positive ANCA, 50％ had poor prognosis.
Ｃｏｎｃｌｕｓｉｏｎ：DNASE1L3 deficiency is more frequent in men with lupus nephritis. Patients with lupus nephritis due to DNASE1L3 deficiency are susceptible to extra-renal involvement of the haematological system, joints, skin, lung and digestive system,as well as positive ANCA. Patients with lupus nephritis with positive ANCA or pulmonary haemorrhage should be carefully questioned about family history. Timely genetic testing should also be performed to consider the possibility of DNASE1L3 deficiency.

Key words: DNASE1L3 gene, lupus nephritis, pathogenic varian, tpulmonary haemorrhage