Elucidation of pathogenesis and development of novel therapy of chilblain lupus on the basis of an exonuclease enzyme

1例日本女性冻疮性狼疮患者家族史被认为是常染色体显性遗传。患者为1岁起病的冻疮性狼疮。她的双侧手指和鼻子上有皮肤溃疡，手指关节有收缩。对TREX1和SAMHD1的所有编码外显子和外显子-内含子边界进行了直接测序。患者有一种新的杂合性错义TREX1c.394C&gt；G(p.Pro132Ala)突变。体外3次单链DNA核酸外切试验表明，TREX1 p.Pro132Ala存在酶活性异常。综上所述，我们首次在日本发现了由TREX1功能障碍引起的家族性冻疮性狼疮。

A Japanese female patient of chilblain lupus followed by us has family history of chilblain lupus which is considered autosomal dominant trait. The onset of chilblain lupus of the patient was 1 year-old. She shows skin ulcers on the bilateral fingers and nose, and has contraction of finger joints. Direct sequencing of all coding exons and exon-intron boundaries of TREX1 and SAMHD1 was conducted. The patient had a novel heterozygous missense TREX1 c.394C>G (p.Pro132Ala) mutation. in vitro 3 prime single stranded DNA exonuclease assay revealed that TREX1 p.Pro132Ala had dysfunction of enzyme activity. Taken together, we found familial chilblain lupus due to TREX1 dysfunction in Japan for the first time.