Partial recessive IFN-γR1 deficiency: genetic, immunological and clinical features of 14 patients from 11 kindreds
Partial recessive IFN-γR1 deficiency: genetic, immunological and clinical features of 14 patients from 11 kindreds
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DOI：
10.1093/hmg/ddr029
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发表时间：
2011-04-15
影响因子：
3.5
通讯作者：
Rodriguez-Gallego, Carlos
中科院分区：
文献类型：
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作者：
Sologuren, Ithaisa;Boisson-Dupuis, Stephanie;Rodriguez-Gallego, Carlos
我们报告了一系列的14例患者从11个隐性部分（RP）-干扰素（IFN）-γ R1缺乏症。在来自智利、葡萄牙和波兰的9名纯合子患者中发现了I87 T突变，在来自加那利群岛的5名纯合子患者中发现了V63 G突变。创始人的影响占这两个突变的复发。I87T和V63G突变患者的最近共同祖先可能分别生活在1600（875 - 2950）和500（200 - 1275）年前。这两个等位基因赋予的表型相似，但在IFN-γ R1水平和对IFN-γ的残留反应方面不同。结核病1例，环境分枝杆菌病6例，卡介苗病6例。一名患者没有患分枝杆菌感染，但有播散性沙门氏菌病，这也存在于其他两名患者。首次环境分枝杆菌病的发病年龄在患者之间差异很大，平均值为11.25 ± 9.13岁。13例患者存活至14.82 ± 11.2岁，1例患者在诊断为长期鸟分枝杆菌感染并开始抗分枝杆菌治疗后9天，于7岁时死亡。多达10名患者目前没有感染，没有预防措施。14例患者的临床异质性与IFNGR1基因型或由此产生的细胞表型没有明显相关性。因此，RP-IFN-γ R1缺乏症比最初认为的更常见，在患有轻度或重度分枝杆菌疾病的儿童和成人中都应考虑。
We report a series of 14 patients from 11 kindreds with recessive partial (RP)- interferon (IFN)-gamma R1 deficiency. The I87T mutation was found in nine homozygous patients from Chile, Portugal and Poland, and the V63G mutation was found in five homozygous patients from the Canary Islands. Founder effects accounted for the recurrence of both mutations. The most recent common ancestors of the patients with the I87T and V63G mutations probably lived 1600 (875-2950) and 500 (200-1275) years ago, respectively. The two alleles confer phenotypes that are similar but differ in terms of IFN-gamma R1 levels and residual response to IFN-gamma. The patients suffered from bacillus Calmette-Guerin-osis (n = 6), environmental mycobacteriosis (n = 6) or tuberculosis (n = 1). One patient did not suffer from mycobacterial infections but had disseminated salmonellosis, which was also present in two other patients. Age at onset of the first environmental mycobacterial disease differed widely between patients, with a mean value of 11.25 +/- 9.13 years. Thirteen patients survived until the age of 14.82 +/- 11.2 years, and one patient died at the age of 7 years, 9 days after the diagnosis of long-term Mycobacterium avium infection and the initiation of antimycobacterial treatment. Up to 10 patients are currently free of infection with no prophylaxis. The clinical heterogeneity of the 14 patients was not clearly related to either IFNGR1 genotype or the resulting cellular phenotype. RP-IFN-gamma R1 deficiency is, thus, more common than initially thought and should be considered in both children and adults with mild or severe mycobacterial diseases.