一种新型的X连锁隐性孟德尔遗传性分枝杆菌病易感性形式。

A novel X-linked recessive form of Mendelian susceptibility to mycobaterial disease.

作者信息

Bustamante Jacinta, Picard Capucine, Fieschi Claire, Filipe-Santos Orchidée, Feinberg Jacqueline, Perronne Christian, Chapgier Ariane, de Beaucoudrey Ludovic, Vogt Guillaume, Sanlaville Damien, Lemainque Arnaud, Emile Jean-François, Abel Laurent, Casanova Jean-Laurent

机构信息

Laboratoire de Génétique Humaine des Maladies Infectieuses INSERM Unité 550, Faculté Necker, Paris, France.

出版信息

J Med Genet. 2007 Feb;44(2):e65. doi: 10.1136/jmg.2006.043406.

DOI:10.1136/jmg.2006.043406

PMID:17293536

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2598058/

Abstract

BACKGROUND

Mendelian susceptibility to mycobacterial disease (MSMD) is associated with infection caused by weakly virulent mycobacteria in otherwise healthy people. Causal germline mutations in five autosomal genes (IFNGR1, IFNGR2, STAT1, IL12RB1, IL12B) and one X-linked (NEMO) gene have been described. The gene products are physiologically related, as they are involved in interleukin 12/23-dependent, interferon gamma-mediated immunity. However, no genetic aetiology has yet been identified for about half the patients with MSMD.

METHODS

A large kindred was studied, including four male maternal relatives with recurrent mycobacterial disease, suggesting X-linked recessive inheritance. Three patients had recurrent disease caused by the bacille Calmette-Guérin vaccine, and the fourth had recurrent tuberculosis. The infections showed tropism for the peripheral lymph nodes.

RESULTS

Known autosomal and X-linked genetic aetiologies of MSMD were excluded through genetic and immunological investigations. Genetic linkage analysis of the X-chromosome identified two candidate regions, on Xp11.4-Xp21.2 and Xq25-Xq26.3, with a maximum LOD score of 2.

CONCLUSION

A new X-linked recessive form of MSMD is reported, paving the way for the identification of a new MSMD-causing gene.

摘要

背景

孟德尔式分枝杆菌病易感性（MSMD）与原本健康的人感染弱毒力分枝杆菌有关。已描述了五个常染色体基因（IFNGR1、IFNGR2、STAT1、IL12RB1、IL12B）和一个X连锁基因（NEMO）中的致病种系突变。这些基因产物在生理上相关，因为它们参与白细胞介素12/23依赖性、干扰素γ介导的免疫。然而，约一半的MSMD患者尚未确定遗传病因。