Early-Onset Invasive Infection Due to Corynespora cassiicola Associated with Compound Heterozygous CARD9 Mutations in a Colombian Patient
Early-Onset Invasive Infection Due to Corynespora cassiicola Associated with Compound Heterozygous CARD9 Mutations in a Colombian Patient
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DOI：
10.1007/s10875-018-0549-0
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发表时间：
2018-10-01
影响因子：
9.1
通讯作者：
Luis Franco, Jose
中科院分区：
文献类型：
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作者：
Arango-Franco, Carlos A.;Moncada-Velez, Marcela;Luis Franco, Jose
目的CARD9缺乏症是一种先天免疫缺陷，使健康人易患皮肤粘膜和侵袭性真菌感染，主要由念珠菌引起，但也有皮肤真菌、曲霉菌和其他真菌引起。表丝菌病是由暗色真菌(褐丝菌)引起的一组新出现的真菌感染，在CARD9缺乏症患者中越来越多地被发现。棒孢霉属属于拟丝孢菌，只有一名成年CARD9缺乏症患者被报道患有由卡西尼科拉引起的侵袭性疾病。我们确定了一名哥伦比亚儿童患有早发性、深部和破坏性的卡西尼科拉粘膜皮肤感染，并寻找CARD9基因突变。进行微生物学检查和活组织检查。进行全外显子测序(WES)和Sanger测序，以证实CARD9在患者及其家系中的突变。用免疫印迹法检测外周血单个核细胞(PBMC)中CARD9蛋白的表达。结果患者左侧面部有一大片硬结、恶臭、疣状溃烂病变，伴有广泛的坏死和结痂，是一种卡氏囊虫感染性疾病。WES在患者中发现了复合杂合性突变，包括先前报道的p.Q289*无义突变(c.865C>；T，外显子6)和一个新的缺失(c.23_29del；p.Asp8Alafs10*)，导致外显子2的框架移位和过早停止密码子。患者外周血单个核细胞中没有CARD9蛋白表达。
PurposeCARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida, but also by dermatophytes, Aspergillus, and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused by dematiaceous fungi (phaeohyphomycetes) and are being increasingly identified in patients with CARD9 deficiency. The Corynespora genus belongs to phaeohyphomycetes and only one adult patient with CARD9 deficiency has been reported to suffer from invasive disease caused by C. cassiicola. We identified a Colombian child with an early-onset, deep, and destructive mucocutaneous infection due to C. cassiicola and we searched for mutations in CARD9.MethodsWe reviewed the medical records and immunological findings in the patient. Microbiologic tests and biopsies were performed. Whole-exome sequencing (WES) was made and Sanger sequencing was used to confirm the CARD9 mutations in the patient and her family. Finally, CARD9 protein expression was evaluated in peripheral blood mononuclear cells (PBMC) by western blotting.ResultsThe patient was affected by a large, indurated, foul-smelling, and verrucous ulcerated lesion on the left side of the face with extensive necrosis and crusting, due to a C. cassiicola infectious disease. WES led to the identification of compound heterozygous mutations in the patient consisting of the previously reported p.Q289* nonsense (c.865C > T, exon 6) mutation, and a novel deletion (c.23_29del; p.Asp8Alafs10*) leading to a frameshift and a premature stop codon in exon 2. CARD9 protein expression was absent in peripheral blood mononuclear cells from the patient.ConclusionWe describe here compound heterozygous loss-of-expression mutations in CARD9 leading to severe deep and destructive mucocutaneous phaeohyphomycosis due to C. cassiicola in a Colombian child.