背景:严重联合免疫缺陷(SCID)是一组致命的原发性免疫缺陷,其特征是T细胞分化严重受损。IL7R缺乏症是SCID的一种罕见形式,通常在生命的头几个月出现严重和机会性感染,未能茁壮成长,除非治疗,否则死亡风险很高。尽管最近通过新生儿筛查在早期诊断方面取得了进步,中国人群中很少有IL7R相关SCID患者的报告.
方法:这里,我们回顾性分析了一个有症状的5个月大女孩的SCID病例,包括严重的T细胞耗竭,反复发烧,口腔溃疡,肺炎,肝脾肿大,骨髓吞噬作用,以及细菌和病毒感染。全外显子组测序(WES),定量PCR(qPCR),和染色体微阵列分析(CMA),以确定患者的遗传病因。我们确定了268kb的缺失和剪接变体,c.221+1G>A,在先证者中。IL7R的这两种变体均遗传自父亲和母亲。
结论:据我们所知,这是SCID患者中完整IL7R基因缺失与致病性剪接变异体的首次报道.这种缺失也扩大了由IL7R引起的SCID的致病变异谱。基于外显子组的拷贝数变异分析的结合使WES成为儿科患者临床诊断的强大分子诊断技术。
Severe combined immunodeficiency (SCID) is a group of fatal primary immunodeficiencies characterized by the severe impairment of T-cell differentiation. IL7R deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infections, failure to thrive, and a high risk of mortality unless treated. Although recent improvements in early diagnosis have been achieved through newborn screening, few IL7R-related SCID patients had been reported in the Chinese population.
Here, we retrospectively analyzed a
case of SCID in a 5-month-old girl with symptoms, including severe T-cell depletion, recurrent fever, oral ulcers, pneumonia, hepatosplenomegaly, bone marrow hemophagocytosis, and bacterial and viral infections. Whole-
exome sequencing (WES), quantitative PCR (qPCR), and chromosome microarray analysis (CMA) were performed to identify the patient\'s genetic etiology. We identified a 268 kb deletion and a splicing variant, c.221 + 1G > A, in the proband. These two variants of IL7R were inherited from the father and mother.
To our knowledge, this is the first report of whole IL7R gene deletion in combination with a pathogenic splicing variant in a patient with SCID. This deletion also expands the pathogenic variation spectrum of SCID caused by IL7R. The incorporation of
exome-based copy number variant analysis makes WES a powerful molecular diagnostic technique for the clinical diagnosis of pediatric patients.