PDF(Sci-hub)
Abstract：
Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) syndrome is a serious autosomal recessive genetic disease. So far, <40 cases have been reported worldwide, and only one case has been reported in China. The main clinical features of SIFD are sideroblastic or microcytic anemia, immune deficiency, and recurrent episodes of inflammation. Here, we describe two unrelated cases of SIFD from China with different clinical manifestations and mild symptoms. Patient 1 was hospitalized at the age of 3.5 years due to persistent joint swelling with imaging of multiple joint effusions. Patient 2 was hospitalized at the age of 12 years due to repeated rashes on both lower limbs and oral ulcers. SIFD was detected using gene testing, which revealed the following compound heterozygous variants in TRNT1 in cases 1 and 2, respectively: c.88A > G/c.363G > T and c.302 T > C/c.1234cC > T. Searches of the HGMD databases revealed that these variants were all novel. Molecular dynamics simulations revealed that the missense variants c.363G > T and c.302 T > C would cause changes in protein structure and thus affect protein function. Finally, through literature reviewing, we found that the mortality in cases of SIFD was approximately 44% (14/32), and about 79% of individuals who died carried the hot-spot mutation c.668 T > C. Moreover, variants in the non-coding region were significantly more common among patients who died than among survivors. Our cases further expand the existing knowledge of the phenotype and variation spectrums of SIFD and suggest that genomic diagnosis is valuable for the hierarchical clinical management of this disease.
摘要：
铁粒幼细胞性贫血伴B细胞免疫缺陷，周期性发烧,发育迟缓(SIFD)综合征是一种严重的常染色体隐性遗传病。到目前为止,全世界已报告<40例，中国只报告了一例。SIFD的主要临床特征是铁粒成细胞或小红细胞性贫血，免疫缺陷，和反复发作的炎症.这里,我们描述了来自中国的两个不相关的SIFD病例，这些病例具有不同的临床表现和轻度症状。患者1在3.5岁时住院，原因是持续性关节肿胀，并进行了多个关节积液的成像。患者2在12岁时因下肢反复出现皮疹和口腔溃疡而住院。使用基因检测检测到SIFD，在病例1和2中分别揭示了TRNT1中的以下复合杂合变体：c.88A>G/c.363G>T和c.302T>C/c.1234cC>T。对HGMD数据库的搜索显示这些变体都是新颖的。分子动力学模拟表明，错义变体c.363G>T和c.302T>C会引起蛋白质结构的变化，从而影响蛋白质功能。最后,通过文献回顾，我们发现SIFD病例的死亡率约为44%(14/32)，大约79%的死亡个体携带热点突变c.668T>C。此外，非编码区变异在死亡患者中明显比在幸存者中更常见.我们的病例进一步扩展了对SIFD表型和变异谱的现有知识，并表明基因组诊断对于该疾病的分层临床管理具有重要意义。
