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NEJM:科学家发现和致死性真菌感染相关的特殊基因

来源:生物谷 2013-11-06 23:55

致死性的真菌感染。

(Credit: Rockefeller University)

2013年11月7日 讯 /生物谷BIOON/ --对于很多人来讲,真菌感染比如足癣仅仅需要去药店买点药就可以搞定,但是在某些时候,真菌感染却可以扩散到皮肤以下,淋巴结、骨头、消化道甚至大脑中;近日,来自内克尔医学院的研究者发现了一种新型的遗传缺陷,其可以使得真菌感染发生严重的扩散,这种扩散被称之为深部皮癣菌病,相关研究成果刊登于国际杂志New England Journal of Medicine上。

该项研究揭示了为何有时候真菌感染疗法会失败,而且为研究者开发相应疗法治疗真菌感染疾病提供了一定思路。研究者Jean-Laurent Casanova表示,他们对17位患深部皮癣菌病但仍然健康的个体进行了全基因组的研究,这些个体的免疫系统可以正常工作,而且可以有效抵御真菌感染。

研究者发现了名为CARD9的特殊基因,此前研究发现其他真菌感染主要是由于该基因缺失导致的,而通过对研究对象进行基因组测序后,研究者发现,CARD9基因确实在患者机体中是缺失的。

研究者Anne Puel说道,我们研究揭示,CARD9基因的缺失是引发深部皮肤癣菌病的原因,早期感染主要发生于儿童时期,此时病人表现出皮肤头癣时,由于病人遗传缺失及损伤的免疫系统,因此其并不能够有效抵御真菌的感染,因此病菌很难被清除出机体,最终引发深度扩散,危害病人健康。

随着研究者的深入研究,他们将给与敏感个体合适的建议以抑制真菌的感染,研究者希望通过深入研究来开发治疗真菌感染的新型疗法,最后研究者表示,对CARD9基因的研究将帮助揭示其在人体抗真菌感染上的角色,从而帮助研究者追踪不同细胞中的信号路径,进而帮助开发抵御感染的疗法。(生物谷Bioon.com)

Deep Dermatophytosis and Inherited CARD9 Deficiency

Fanny Lanternier, M.D., Saad Pathan, Ph.D., Quentin B. Vincent, M.D., Luyan Liu, M.Sc., Sophie Cypowyj, Ph.D., Carolina Prando, M.D., Ph.D., Mélanie Migaud, B.S., Lynda Taibi, M.D., Aomar Ammar-Khodja, M.D., Omar Boudghene Stambouli, M.D., Boumediene Guellil, M.D., Frederique Jacobs, M.D., Ph.D., Jean-Christophe Goffard, M.D., Ph.D., Kinda Schepers, M.D., Ph.D., Véronique del Marmol, M.D., Ph.D., Lobna Boussofara, M.D., Mohamed Denguezli, M.D., Molka Larif, M.D., Hervé Bachelez, M.D., Ph.D., Laurence Michel, Ph.D., Gérard Lefranc, Ph.D., Rod Hay, M.D., Ph.D., Gregory Jouvion, Ph.D., Fabrice Chretien, M.D., Ph.D., Sylvie Fraitag, M.D., Marie-Elisabeth Bougnoux, M.D., Ph.D., Merad Boudia, M.D., Laurent Abel, M.D., Ph.D., Olivier Lortholary, M.D., Ph.D., Jean-Laurent Casanova, M.D., Ph.D., Capucine Picard, M.D., Ph.D., Bodo Grimbacher, M.D., Ph.D., and Anne Puel, Ph.D.

Background 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. Methods 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. Results 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. Conclusions All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency.

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