一例TRNT1基因复合杂合新变异导致儿童SIFD综合征CSCD

目的对1例铁粒幼红细胞性贫血伴B细胞免疫缺乏、周期性发烧和发育迟缓患儿进行TRNT1基因变异分析,明确其可能的遗传学病因。方法应用外显子组检测对患儿及父母进行基因分析,对与临床表型相关的可疑变异位点进行Sanger验证及相关生物信息学预测分析其生物危害性,并通过同源结构预测变异危害性。结果基因检测结果显示患儿TRNT1基因存在c.88A>G(p.Met30Val)和c.363G>T(p.Glu121Asp)复合杂合变异,经Sanger测序验证父亲携带c.88A>G(p.Met30Val)杂合变异,母亲携带c.363G>T(p.Glu121Asp)杂合变异。检索PubMed等数据库两个变异均未见报道。通过对p.Glu121Asp蛋白结构预测分析变异可能会影响TRNT1蛋白与tRNA的结合稳定性。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,TRNT1基因c.88A>G和c.363G>T变异分别判定为意义不明确(PM2+PP3+PP4)和可能致病性变异(PM1+PM2+PP3+PP4)。结论TRNT1基因c.88A>G(p.Met30Val)和c.363G>T(p.Glu121Asp)复合杂合变异可能为该患儿发病原因,新变异的检出拓展了TRNT1基因的变异谱。

A case of SIFD syndrome caused by novel compound heterozygous variants of TRNT1 gene

Objective To detect variant of TRNT1 gene in a child featuring sideroblastic anemia with B-cell immunodeficiency, periodic fever and developmental delay (SIFD). Methods The proband and his parents were analyzed through trio-whole exome sequencing. Sanger sequencing and bioinformatic analysis were carried out to verify the candidate variant sites associated with the clinical phenotype. Results Genetic testing showed that the proband has carried compound heterozygous variants of the TRNT1 gene, namely c. 88A>G (p.Met30Val) and c. 363G>T (p.Glu121Asp). Sanger sequencing confirmed that the variants were respectively inherited from his father and mother. The variants were unreported previously. By bioinformatic analysis, both variants were predicted to affect the stability of binding of the TRNT1 protein with tRNA. Based on the American College of Medical Genetics and Genomics standards and guidelines, c. 88A>G and c. 363G>T variants of TRNT1 gene were predicted to be uncertain significance (PM2+ PP3+ PP4) and likely pathogenic(PM1+ PM2+ PP3+ PP4), respectively. Conclusion The c. 88A>G (p.Met30Val) and c. 363G>T (p.Glu121Asp) compound heterozygous variants of the TRNT1 gene probably underlay the disease in this patient. Above finding has enriched the spectrum of TRNT1 gene variants. © 2021 West China University of Medical Sciences. All rights reserved.