Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare congenital condition characterized by a selective predisposition to infections caused by weakly virulent mycobacteria and other types of intra-macrophagic pathogens. The 16 genes associated with MSMD display a considerable level of allelic heterogeneity, accounting for 31 distinct disorders with variable clinical presentations and prognosis. Most of MSMD deficiencies are isolated, referred to as selective susceptibility to mycobacterial diseases. However, other deficiencies are syndromic MSMD, defined by the combination of the mycobacterial infection with another, equally common, infectious, specific phenotypes. Herein, we described a series of 32 Iranian MSMD cases identified with seven distinct types of molecular defects, all of which are involved in the interferon gamma (IFNγ) immunity, including interleukin IL-12 receptor-β1 (IL-12Rβ1) deficiency (fifteen cases), IL-12p40 deficiency (ten cases), and IL-23R deficiency (three cases), as well as IFNγ receptor 1 (IFNγR1) deficiency, IFNγ receptor 2 (IFNγR2) deficiency, interferon-stimulated gene 15 (ISG15) deficiency, and tyrosine kinase 2 (TYK2) deficiency each in one case. Since the first report of two MSMD patients in our center, we identified 30 other affected patients with similar clinical manifestations. As the number of reported Iranian cases with MSMD diagnosis has increased in recent years and according to the national vaccination protocol, all Iranian newborns receive BCG vaccination at birth, early diagnosis, and therapeutic intervention which are required for a better outcome and also prevention of similar birth defects. Therefore, we investigated the clinical and molecular features of these 32 patients. The current report also defined novel classes of pathological mutations, further expanding our knowledge of the MSMD molecular basis and associated clinical manifestations.

对分枝杆菌疾病 (MSMD) 的孟德尔易感性是一种罕见的先天性疾病，其特征是对由弱毒力分枝杆菌和其他类型的巨噬细胞内病原体引起的感染的选择性易感性。与 MSMD 相关的 16 个基因显示出相当程度的等位基因异质性，占 31 种不同的疾病，具有不同的临床表现和预后。大多数 MSMD 缺陷是孤立的，称为对分枝杆菌疾病的选择性易感性。然而，其他缺陷是综合征性 MSMD，定义为分枝杆菌感染与另一种同样常见的传染性特定表型的组合。在此，我们描述了一系列 32 例伊朗 MSMD 病例，这些病例被确定为具有七种不同类型的分子缺陷，所有这些都涉及干扰素γ（IFNγ）免疫，包括白细胞介素IL-12受体-β1（IL-12Rβ1）缺乏（15例）、IL-12p40缺乏（10例）和IL-23R缺乏（3例） )，以及 IFNγ 受体 1 (IFNγR1) 缺陷、IFNγ 受体 2 (IFNγR2) 缺陷、干扰素刺激基因 15 (ISG15) 缺陷和酪氨酸激酶 2 (TYK2) 缺陷各一种。自我们中心首次报告两名 MSMD 患者以来，我们确定了 30 名其他具有相似临床表现的患者。由于近年来伊朗报告的 MSMD 诊断病例数有所增加，根据国家疫苗接种协议，所有伊朗新生儿在出生时都接受卡介苗接种，早期诊断，和治疗干预，这是获得更好结果和预防类似出生缺陷所必需的。因此，我们调查了这 32 名患者的临床和分子特征。目前的报告还定义了新的病理突变类别，进一步扩展了我们对 MSMD 分子基础和相关临床表现的了解。