Coinheritance of generalized pustular psoriasis and familial Behcet-like autoinflammatory syndrome with variants in IL36RN and TNFAIP3 in the heterozygous state
Coinheritance of generalized pustular psoriasis and familial Behcet-like autoinflammatory syndrome with variants in IL36RN and TNFAIP3 in the heterozygous state
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全身性脓疱型银屑病与家族性白塞样自身炎症综合征的共同遗传（IL36RN 和 TNFAIP3 杂合状态下存在变异）
DOI：
10.1111/1346-8138.15034
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发表时间：
2019-07-29
影响因子：
3.1
通讯作者：
Yao, Zhirong
中科院分区：
文献类型：
--
作者：
Liang, Jianying;Zhang, Hui;Yao, Zhirong
泛发性脓疱性银屑病（GPP）目前已知是由IL36RN中的双等位基因变体和CARD 14和AP1S3中的单等位基因变体引起的。存在修饰基因座或寡基因遗传已被假设。我们报告了一个病人的独特的共同遗传的致病性变异IL36RN（c.115+6T>C）和TNFAIP3（c.547C>T，p.R183*）导致遗传实体GPP和家族性白塞样自身炎症综合征（AISBL）。通过桑格测序鉴定的IL 36 RN中的杂合变体遗传自其未受影响的父亲，而通过全外显子组测序检测到TNFAIP 3中的杂合变体，并且还在患者的AISBL受影响的母系亲属中鉴定。需要进一步的功能研究来研究TNFAIP3的变体是否在GPP的发展中起作用，或者仅仅导致白塞氏病表型。然而，我们的数据表明，GPP中IL36RN基因杂合携带者的全外显子组测序可用于寻找潜在的第二遗传位点。
Generalized pustular psoriasis (GPP) is now known to be caused by biallelic variants in IL36RN and monoallelic variants in CARD14 and AP1S3. The presence of a modifier locus or oligogenic inheritance have been hypothesized. We report on a patient with a unique coinheritance of pathogenic variants in IL36RN (c.115+6T>C) and TNFAIP3 (c.547C>T, p.R183*) causing the genetic entities GPP and familial Behcet-like autoinflammatory syndrome (AISBL). The heterozygous variant in IL36RN identified by Sanger sequencing was inherited from his unaffected father, while the heterozygous variant in TNFAIP3 was detected by whole-exome sequencing and was also identified in the patient's AISBL-affected maternal relatives. Further functional studies are required to research whether the variant of TNFAIP3 plays a part in the development of GPP or simply causes the Behcet's disease phenotype. However, our data suggest that whole-exome sequencing for the heterozygous carrier of the IL36RN gene in GPP be used to find the potential second genetic locus.