Deep dermatophytosis and inherited CARD9 deficiency.
Deep dermatophytosis and inherited CARD9 deficiency.
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DOI：
10.1056/nejmoa1208487
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发表时间：
2013-10-31
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影响因子：
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通讯作者：
Puel A
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作者：
Lanternier F;Pathan S;Vincent QB;Liu L;Cypowyj S;Prando C;Migaud M;Taibi L;Ammar-Khodja A;Stambouli OB;Guellil B;Jacobs F;Goffard JC;Schepers K;Del Marmol V;Boussofara L;Denguezli M;Larif M;Bachelez H;Michel L;Lefranc G;Hay R;Jouvion G;Chretien F;Fraitag S;Bougnoux ME;Boudia M;Abel L;Lortholary O;Casanova JL;Picard C;Grimbacher B;Puel A
深部皮肤真菌病是一种严重的，有时危及生命的真菌感染引起的皮肤真菌。其特征是广泛的真皮和皮下组织浸润，并经常扩散到淋巴结，偶尔也扩散到中枢神经系统。这种情况不同于常见的浅表皮肤真菌感染，并已报告在患者没有已知的免疫缺陷。患者大多来自北非，血缘，多重家庭，这强烈表明孟德尔遗传原因。我们研究了来自8个无关的突尼斯、阿尔及利亚和摩洛哥家庭的17例无免疫缺陷的深部皮肤真菌病患者的临床特征。由于CARD9（含半胱天冬酶募集结构域蛋白9）缺陷已在伊朗家庭与侵袭性真菌感染的报道，我们也测序CARD9的患者。4名患者死亡，年龄分别为28、29、37和39岁，临床上患有活动性深部皮肤真菌病。在存活的患者中没有报告其他严重感染，真菌或其他感染，年龄范围为37至75岁。来自7个不相关家族的15名阿尔及利亚和突尼斯患者由于创始人效应而具有纯合Q289X CARD9等位基因。这2名摩洛哥同胞是R101C CARD9等位基因纯合子。这两个等位基因都是罕见的有害变体。这些等位基因的家族分离符合常染色体隐性遗传和完全临床遗传。所有深部皮肤真菌病患者均为常染色体隐性遗传CARD9缺陷症。深部皮肤真菌病似乎是CARD9缺乏症的重要临床表现。（由国家研究机构和其他机构供资）
Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain–containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.)